TWI328584B - Imidazole derivatives - Google Patents

Description

1328584 A7 B7 V. INSTRUCTION DESCRIPTION OF THE INVENTION (1) The present invention relates to a compound having the following formula

Wherein A is phenyl, pyridin-2-yl, pyridin-3-yl or piperidin-1-yl; RVR2 are each independently hydrogen, halogen, lower alkyl, cycloalkyl, lower carbon, trifluoro Mercapto,-0-trifluoromethyl'-S-trifluoromethyl, S-lower alkyl, lower alkoxy, -CHF2, -C(lower alkyl)f2, -CHF2, stupid , nitro, decyloxy, hydroxy or amine group or formed together with carbon atoms attached to any adjacent position - ch=ch-ch=ch-, -ch=ch-ch=n-,-(ch2)3 -,- O-CHrO- ' _0_CF2_0- ' -CH2_0-CH2· or · ch2ch2-o-; R3 is hydrogen, lower alkyl, cycloalkyl, phenyl, S-lower alkyl, amine, low Carboalkyl-amino, -NHC(O)-lower alkyl or hydroxy-lower alkyl; r4/r5 are each hydrogen or lower alkyl or together with the carbon atom to which they are attached - (ch2) 4-; r6/r6' are each hydrogen or lower alkyl; -5- This paper scale applies to Chinese National Standard (CNS) A4 specification (210X297 mm)

Binding

Line 1328584 A7, B7 V. Description of invention (2) X is -N<!-t-; Y is =N-, -NH-, -N=CH- or -CH=; Z is -CR = 9 -N = ' -NR.^- 1 -N-CR^- * =CH- N=C(R7)- or =N-CH=CH-; R7 is nitrogen, .-CH2OH or low carbon alkyl; *·· n is Ο ! 1 or 2 ; m is 0 or 1; and the dotted line can be a bond; and its pharmaceutically acceptable acid addition salt. Heterocyclic aromatic group of formula I

Has the following structural formula:

Therefore, this formula I covers the following types of compounds:

-6- This paper scale applies to China National Standard (CNS) Α4 specification (210 X 297 mm) 1328584 A7 B7 V. Description of invention

Lc Id

Each substituent is as described above. The compounds of formula I and their salts are valuable therapeutically distinct. The compound of the present invention is a NMDA (N-mercapto-D-aspartate) receptor subtype selective interrupting agent, which acts as a key function in neuronal activity and formation, and thus mediates the central nervous system. Potential developmental processes and play a key role in learning and memory formation. In the pathological condition of acute and chronic forms of neurodegeneration, NMDA receptors have been used in this paper size. The S standard (CNS) A4 specification (210 X 297 mm) 1328584

Activation is a key to the initiation of neuronal cell death. The eNMDA receptor system consists of members of the second subunit group, that is, NR-1 originating from different genes (8 different split variants and NR-2 (A to D) )»The members of this two sub-unit population are shown to be distributed in different areas of the brain. The non-homogeneous combination of different NR 2 subunits of the members of the dichotomy resulted in different medical properties of the NMDA receptor. Possible therapeutic indicators for NMDA NR-2B receptor subtype specific occlusion agents include, for example, acute neurodegenerative forms due to stroke and brain trauma, as well as chronic neurodegenerative forms such as Alzheimer's disease, Parkinson's disease , Huntington's disease, ALS (muscle atrophic lateral sclerosis), and neurodegenerative diseases caused by bacterial or viral infections, in addition to depression and chronic and acute pain. The object of the present invention is the preparation of a compound of the formula I and a pharmaceutically acceptable acid addition salt thereof, a compound of the formula I and a salt thereof, a medicament containing a compound of the formula I or a pharmaceutically acceptable acid addition salt thereof, and The compounds of formula I and their pharmaceutically acceptable salts are useful for the control or prevention of diseases, particularly the various diseases and conditions cited above, as well as for the individual manufacture of corresponding drugs. The present invention encompasses racemic mixtures and their corresponding enantiomers. The general term definitions used hereinafter as used herein are applicable regardless of whether the term appears alone or in combination. The term "lower alkyl J" as used herein denotes a straight or branched alkyl group having 1 to 7 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, etc. Lower alkyl group having 1 to 4 carbon atoms" As used herein, the term "lower alkenyl group" means a C2-C7 carbon group and contains at least one double bond in the chain. The term "halogen atom" means gas, broken, fluorine and desert. -8- The paper size is based on the Chinese National Standard (CNS) A4 specification (210X 297 mm)

Binding

1328584 A7 B7 V. INSTRUCTIONS (5) — The term "lower alkoxy" means a radical in which the radicals are as defined above and the alkyl radicals are bonded through an oxygen atom. "Cyclosyl" - a word means a carbocyclic ring having 3 to 6 carbon atoms, preferably a propyl group. The term "pharmaceutically acceptable acid addition salt" encompasses salts formed with inorganic and organic acids such as hydrochloric acid, nitric acid, sulfuric acid, dish acid, citric acid 'formic acid, fumaric acid, butylene Diacid, acetic acid, succinic acid, tartaric acid, decane-sulfonic acid, p-toluenesulfonic acid, and the like. Preferred compounds of formula I are those wherein A is a phenyl group such as the group consisting of:

Wherein rVr2 is each hydrogen 'halogen atom' low carbon alkyl, trifluoromethyl 'S-lower alkyl, lower alkoxy, _〇CHF2, phenyl, nitro, benzyloxy, hydroxy or amine The base or the carbon atom to which it is attached is formed as -(CH2)3-, -〇-ch2-〇-, -CH2-0-CH2- or -CH2CH2-0-; R3 is hydrogen 'low carbon leuco' Base, S-low carbon alkyl, amine, low carbon, fenyl-amine, -NHC (〇)-low carbon ray or warp-low -9 - This paper scale applies to China National Standard (CNS) A4 Specification (210X 297 public) ^28584 V. Description of the invention (ethyl-, 1H-imidazole, chloro-3-indenylphenyl)_m ethyl-, imidazol-4-yl]methyl]-2. ...(三气曱基)phenyl]-gas_3_mercaptophenyl)·1Η•咪心基methyl]ιη·咪唾2美_ 1Η"米唆,卜[[1-[3-( 1,1-Dimethyl-,ethyl)phenyl]-1Η-°m-ol-4-yl]methyl 1 Η-imidazole, difluoroindolyl 4 phenyl)·1Η•imidazole _4• group 2-methyl- or 1-imidazole, 1-[[l-[3-(i,i-methyl]-2-methyl-.yl]-fluoroethyl)-4-fluorophenyl]-1Η- Imidazole _4·yl] is further preferably a compound of the formula

Wherein A is a phenyl group, R1 and R2 are a halogen atom, R3 is a lower alkyl group or hydrogen, and R4, R5 and R0, and R6 is hydrogen, for example, a compound of the formula: ^(3,4-di-phenyl) 3-(2-mercapto-imidazol-1-yl-indenyl)-1Η-pyrazole. •11 - This paper scale applies to China S standard (CNS) Α4 specification (210 X 297 mm) 1328584 A7 __- ·_____B7 V. Description of invention (8) The formula I is further preferably a compound of the formula

Wherein A is a phenyl group, R1 and R2 are a halogen atom, R3 is a lower alkyl group or hydrogen, and R4, R5 and R6 are a hydrogen such as a compound of the formula: 1-(3,4-di-phenyl-phenyl) )-4-imidazolium-1-yl-methyl]H-pyrazole or di(3,4-dioxa-phenyl)-4-mercapto-imidazolyl-indenyl)-m-pyrazole. Further preferred in the scope of Formula I is a compound of the formula

Wherein A is a stupid group, R1 and R2 are a halogen atom, hydrogen, CF3 or a lower alkyl group, R3 is a lower carbon group or hydrogen, and R4, R5 and V, R6 are hydrogen such as a compound of the formula: 1H- Imidazole, 2-mercapto-1-[[4-[3-(trifluoromethyl)phenyl]_1H imidazolyl-2-yl] fluorenyl]-, 1H-imidazole, 1-[[4-(4-fluoro -3-fluorenylphenyl)_1H_carbazole-2-yl]decyl-2-methyl-, 1H- miso, 1-[[4-(3,4-monophenyl)-1Η- Taste salino_2_yl]decyl-2-methyl- or -12- This paper scale applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 1328584 A7 B7 V. Description of invention (9) 1H-imidazole, 4-(4-Fluoro-3-indolylphenyl)_2-(1Η·imidazole)·yl-fluorenyl) Further preferred in the formula I is a compound of the formula

Wherein Α is phenyl, R 1 and R 2 are lower alkyl, halogen or R 3 is lower alkyl or hydrogen ' and R 4 , R 5 and R 6 , R 6 are hydrogen such as a compound of the formula: 3-(3, 4-dimercapto-phenyl)_5·(2_mercapto-oxime small group_methyl)_pylotidine, 3 (4-fluoro-3-indolyl-yl)-5-(2-oxime Base, taste, salino-1 -yl-methyl) than bite, gas-3-methyl-phenyl)-5-(2-mercapto-yttrium-1-yl-indenyl) than bite, 3-( 3-ox-4-cyclo-phenyl)-5-(2-mercaptoisosyl-1 -yl-indenyl) than bite or 3 (4-a-3-difluoroindolyl-phenyl)-5 -(2-曱基米〇^-1_yl_methyl) than bite. Further preferred in the scope of Formula I is a compound of the formula

Wherein hydrazine is a phenyl group, R1 and R2 are a halogen atom, R3 is a lower alkyl group and R4, and R6, and R6. is a hydrogen such as a compound of the formula:

line

V. DESCRIPTION OF THE INVENTION (10 (3'4~-gas-stupyl)-2-(2-mercapto-smellyl)-acridine; the formula 1 is further preferably a compound of the formula

Ig wherein A is phenyl' Ri and R2 is a halogen atom, R3 is a lower alkyl group and r4, rS and R, and R0 is hydrogen, for example, a compound of the formula: 2-(3,4-di-phenyl)_4 -(2-Methyl-ampazole small fluorenyl)-pyridine. Further preferred range of formula I is further a compound wherein A is pyridin-2- or 3-yl or A is piperidinyl-bry. The foregoing compounds of formula I can be made in accordance with the present invention by a) a compound of the formula

Binding

[This paper scale applies to China Retained Home (CNS) A4 specification (210X 297 mm) -14- 1328584 A7 B7

Binding

Line 1328584 V A7 B7-, invention description (12) wherein A is phenyl or pyridin-2- or 3-yl' RJ-R7 is as defined above and hal is bromine or gas, or b) is cleaved by a compound of the formula Protective base

Obtaining a compound of the formula

Binding wherein A and RLR6 are as defined above and PgN protecting groups such as 2-(tridecyldecane)-ethoxylated, or c) a compound of the formula

VIII or

IX -16· This paper scale applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 1328584 A7 B7

1328584 A7 ____; _ B7 V. Description of the invention (14) wherein A is phenyl or pyridin-2- or 3-yl and rLr6 is as defined above and hal is gas or desert, and if desired, the resulting compound of formula I is converted Further details of the preparation of the compound of formula I will be described hereinafter. According to the foregoing variants and using the reaction of the following formula, Figure 1_1, the compound of formula I can be prepared by a known procedure, the preparation procedure being exemplified as follows: According to method step a) 'Sodium hydride is added to the imidazole compound of formula V such as 2-propylimidazole , 2-methylimidazole, imidazole, 4-methylimidazole or a solution of 4,5,6,7-tetrahydrobenzimidazole in DMF. After 30 minutes at room temperature, the mixture is cooled in an ice bath, and a compound of formula II, III or IV such as 4- gas decyl-1-(3,4-di-phenyl)-1 hydrazine-azole is added, 4 - gassulfonyl-1-(3,4-dioxa-phenyl)-1Η-pyrazole or 4-mercapto-1-(3,4-dichloro-phenyl)-3-indolyl-1H - Imidazole. As a result, the resulting mixture was stirred at room temperature for 30 minutes. After evaporation of the solvent, the compound of formula la, lb and Ic was obtained in a conventional manner. Compounds of formula Id can be prepared according to variant b). Compounds of formula VI, for example 1H-imidazole, 2-[(2-indolyl-1H-imidazol-1-yl)methyl]-4-[3-(trifluoromethyl)phenyl]-1-[[2- (trimethyldecyl)ethoxy]indolyl] or oxime imidazole, 4-(4-fluoro-3-indolylphenyl)-[(2-methyl-1H-imidazol-1-yl)methyl ]-l-[[2-(Trimethyldecyl)ethoxy]methyl] was dissolved in ethanol and treated with hydrochloric acid. The reaction mixture was refluxed overnight, cooled to room temperature, concentrated and purified. The compound of the formula If, Ig or Ih is prepared according to the modification method C) as follows: a compound of the formula V such as 2-propylimidazole, 2-methylimidazole, imidazole or 4- is added to a suspension of sodium hydride in mineral oil and DMF. Mercaptoimidazole. The mixture was stirred at room temperature for 15 hours. Then add the compound of formula VIII, IX or X, and heat the mixture to about 1 〇〇 4 -18 - the paper silver scale universal t solid standard (CNS) A4 specification (2l 〇 x 297 public)

Binding

Line 1328584 A7 • B7 V. Inventive Note (16) wherein R1 and R2 are as previously described and DIBAH is diisobutylaluminum hydride and LAH is lithium aluminum hydride. Reaction diagram 2

The substituents R1 to R5 and R7 are as previously described and LAH is lithium aluminum hydride. In the compound of the formula XV, the phenyl group may be substituted with a pyridine-2- or 3-yl group to give a corresponding compound of the formula la. -20- This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1328584

0〆 R2 XX

A7 B7 V. Description of invention (17) Reaction diagram 3

NBS,

A old N

R3 3XC

The substituents R1 and R5 of NaH, R v R Ib1 are as previously described, and NBS is N-bromobutadienimide and AIBN is azo-hydrazine-isobutyronitrile. In the compound of the formula XX, the phenyl group may be substituted with a pyridine-2- or 3-yl group to give a corresponding compound of the formula lb. Reaction Figure 4

-21 - This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 public)

1328584 A7 B7 V. INSTRUCTION DESCRIPTION (18) Substituents R1 to R5 are as previously described and THF is tetrahydrofuran. In the compound of the formula XXIII, the strepyl group may be substituted with a pyridin-2- or 3-yl group to obtain a corresponding compound of the formula Ic. Reaction Figure 5

NaH

XXIV 2. 2·(trimethyldecyl) ethylene methyl gas

The substituents R1 to R5 are as previously described and DMF is N,N-dimethylformamide.

Binding

In the compound of the formula XV, the phenyl group may be substituted with a pyridin-2- or 3-yl group to obtain a compound of the corresponding formula Id. -22- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 B7 V Invention description (19 ) Reaction diagram 6

The substituents R1 to R5 and R7 are as described above and LAH is lithium aluminum hydride. Additional compounds of formula XV may be formulated by the compound

Line replacement. In the compound of formula XV, the phenyl group can be replaced by a p-but-2- or 3-yl group to give a corresponding compound of formula Ie. -23- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 B7

1328584 A7 B7 V. INSTRUCTIONS (21) Reaction Figure 8

The substituents R1 to R5 are as described above and LAH is lithium aluminum hydride. In the formula XV compound, the phenyl group can be substituted with a pyridine-2- or 3-yl group to give a corresponding compound of the formula Ig.

Reaction Figure 9

-25- This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 B7 V. Description of invention (22) The substituents are as described above and BINAP is 2,2,-贰 (diphenyl) Phosphyl)-1, Γ-Linkai. Reaction diagram 10

In formula XV or other compounds, the phenyl group may be replaced by a pyridin-2- or 3-yl group. As described above, the compound of the formula I and its pharmaceutically useful acid addition salt have valuable pharmacodynamic properties. It is a NMD Α receptor subtype 2 Β selective occluder ’ which plays a key role in the regulation of neuronal activity and formation, and therefore plays a key role in the development of the underlying central nervous system and learning and memory formation. The compounds are based on the following studies. Test method! E-Ro 25-6981 Binding (Ro 25-698 1 is [R-(R*,s*)]_ a-(4-hydroxy-phenyl)-cold·indolyl-4-(phenyl) -Methyl)-1 - pyridine propyl alcohol) A male Flintoff albino rat weighing 150-200 g. Use the whole brain to deduct the cerebellum and ventilate the brain in 25 times volume cold Tris-Hc丨5〇mM, EDTA 10 mM 'pH 7.1 buffer using 宝丽冲(p〇lytr〇n) (1〇〇〇〇Γριη, 30 Second) homogenization to prepare the film. The homogenate was centrifuged at 48,000 g for 10 minutes at 4eC. The pellets were resuspended in a volumetric buffer using Polaroid and homogenized at 37 «C

Binding

Line -26-

1328584 A7 B7

Breed for 10 minutes. After centrifugation, the pellets were homogenized in the same buffer at _8 Torr.匚 Freeze for at least 16 hours but no more than 1 day. For binding assay analysis, homogenization: Thaw at 37 eC, centrifugation, and pellets washed three times in Tris_HC1 5 mM, pH 7 4 cold buffer. The pellet was finally resuspended in the same buffer and used at a final concentration of 200 mg protein/ml. The '3H-Ro binding assay was performed using Tris_HCl 50 mM, pH 7.4 buffer. As for the replacement test, '5 nM 3H-Ro 25-6981 was used, and 1 mM mM tetrahydroiso was used. Quin B forest measures non-specific binding, usually accounting for the total amount. Incubation time was 2 hours at 4C' Filtering abort assay analysis on whatmann GF/B glass fiber transition membrane (Unifilter-96' Packard, Inc., Zurich, Switzerland). The filter membrane was washed 5 times with cold buffer. The radioactivity of the filter membrane was counted on a Parker table count microplate scintillation counter after the addition of 40 ml of microscint 40 (Canberra Packard, Inc., Zurich, Switzerland). Compound effects were measured using at least 8 concentrations and repeated at least once. The pooled normalized values were analyzed using a non-linear regression calculation program to obtain IC5() with its relative 95% confidence upper and lower limits.

Binding f The compound of the preferred formula I tested according to the above method (: 5 () (μΜ) is less than 〇. 1 μΜ ° The following table shows several binding activity data: Example number IC5〇 (mM) Example number ICsn (uM ) 1 0.007 151 0.014 2 0.01 152 0.01 3 0.012 153 0.02 4 0.017 154 0.048 -27- This paper scale adopts Chinese g standard (CNs) A4 specification (210X297 mm) 1328584 A7 B7 V. Invention description (24 6 0.045 155 0.01 10 0.004 156 0.014 11 0.005 157 0.014 12 0.008 158 0.041 13 0.095 159 0.014 16 0.009 160 0.016 17 0.012 161 0.05 21 0.043 162 0.016 24 0.016 163 0.017 27 0.027 164 0.03 39 0.043 165 0.046 48 0.061 166 0.02 52 0.078 168 0.038 58 0.093 170 0.039 87 0.017 172 0.024 89 0.048 173 0.028 93 0.02 174 0.063 94 0.021 176 0.032 103 0.043 177 0.0375 105 0.001 178 0.074 109 0.085 180 0.05 111 0.011 181 0.053 119 0.046 183 0.052 130 0.065 186 0.052 -28-

Binding

Line paper size applies to China National Standard (CNS) A4 size (210X 297 mm) 1328584 A7 • B7 V. Inventions and descriptions (25) 136 0.08 189 0.053 139 0.065 192 0.055 140 0.04 194 0.079 141 0.039 199 0.098 143 0.0073 224 0.01 144 0.038 225 0.01 145 0.054 226 0.02 146 0.008 227 0.03 147 0.0092 229 0.012 149 0.0082 230 0.084 150 0.0135 232 0.04 As described herein, the compounds of the formula I and their salts can be admixed in standard pharmaceutical dosage forms, for example with conventional medicines The agent material is administered orally or parenterally, and the adjuvant material is, for example, an organic or inorganic inert carrier material such as water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oil, gum, polyalkylene glycol and the like. The pharmaceutical preparations can be used in solid dosage forms such as tablets, suppositories, capsules, or in liquid dosage forms such as solutions, suspensions or emulsions. Medical adjuvant materials may be added, including preservatives, stabilizers, wetting or emulsifying agents, varying osmotic pressure or salts as buffering agents. Medicinal preparations also contain other therapeutically active substances. Dosages can vary within wide limits, and of course must be tailored to individual case requirements. For oral administration, the dosage is in the range of about 1 mg to about 1000 mg of the compound of formula I per dose, but may be exceeded if applicable. The following examples illustrate further details of the invention. However, these examples are not limited to the scope of the present invention. The paper is based on the Chinese National Standard (CNS) A4 specification (210X 297 mm). 5. Inventions and Descriptions (26) Not limited to the scope of the present invention. All temperatures are expressed in degrees Celsius. Example 1 jH-Feng spray,]-|·|·1·(3,4-diphenyl)-ιη·哞 bit·4-very) A certain ι·2_propyl-hydrochloric acid 肄Π sodium hydride ( 0. 44 grams of 55% in mineral oil dispersion, 10 millimoles) was slowly added to a solution of 2·propylidene (0.55 grams, 5 millimoles) in DMF. After 30 minutes at 2 ° C, the mixture was cooled in an ice bath, and 4_methanol (3 4 • 2 gas phenyl)-1 Η-imidazole (1.0 g, 4 mmol) was added in one portion. The resulting mixture was mixed for 30 minutes at 2 Torr. After evaporation of the solvent, the residue was dissolved in ethyl acetate, washed with water, washed with water, sodium sulfate, and chromatographs, hexanes, methane to 5% (methane, methanol/aqueous ammonium hydroxide = 90: 1〇: 1) Gradient elution]. The free state of the title compound was obtained as a brown oil. (1.12 g ' 84%). After the treatment with hydrochloric acid in methanol solvent followed by diethyl ether, the title compound was isolated as white crystalline material. Melting point 241-243 ° C (methanol / hexane), MS: m / e = 334 (M + ). Examples 2 to 9 were prepared according to the procedure outlined in Example 1. Example 2 Shangji Erwei sniffing 'Wn-(3,4-digas jasmonium-4-) A certain 1-2 methyl-, hydrochloride Π: 2) 2-methylimidazole and sodium hydride The reaction is followed by subsequent treatment with 4_g-mercaptodiuret-phenyl)-indole-imidazole, followed by extraction and subsequent chromatography to give the title compound freeness which is converted to white salt. Melting point > 25 ° C (melanol / diethyl ether), MS: m / e = 306 (M +). Example 3 1H-mimi' 1-[[1-(3,4-diphenyl)-ih-imidazole_4_yl)methyl]-2-ethyl-30- This paper scale applies to S countries Standard (CNS) A4 specification (210X 297 public)

Base-, hydrochloride (1:2) 2 ethyl rice bran reacted with sodium hydride, followed by 4-methylmethyl small (a di-phenyl)-1 Η-imidazole followed by extraction followed by treatment and layer After the analysis, the problem was obtained. A free base which is converted to its white hydrochloride. Melting point > 25 〇 C (sterol/J puzzle), MS: m/e = 320 (M+). Example 4 1H rice sniffing, i_[[i_(3'4-diphenyl)-1H imino-4-yl)methyl]•mercaptoethyl)-, hydrochloride (1:2) 2-isopropyl The imidazole is reacted with sodium hydride, followed by 4 - gas methyl + (3 + di- phenyl) 1-indole - imidazole, followed by extraction and subsequent chromatography to obtain the title compound free base, which is transferred Into its white hydrochloride. Melting point 236-238 ° C (decomposition) (methanol / diethyl ether), Ms: m/e = 335 (M+H+). Example 5 1H-imidazole, i-(3,4-diphenyl)-4-(ι_Η-imidazol-1-yl-indenyl)-, hydrochloride (1:2) rice bran reacted with sodium hydride, then Follow-up treatment with 4_gas thiol_1·(3,4_di-phenyl-phenyl)· ΐΗ· 味 吐 'after extraction and after chromatography, the title compound free base was obtained, which was converted into white Hydrochloride. Melting point > 25 (rc (methanol / diethyl ether), MS: m / e = 292 (M +). Example 6 jjl - taste saliva, 1- (3, 4- two gas stupid) · 4 · "(4-A a-1H-imidazole-1-, A; L_, hydrochloride (I:2) and 1Η-spazole, ΐ-η,4-二窗.笑篡)-4-Γ(5-甲其-1Η-imidol-1-yl)methyl μ, hydrochloride (1:2吖 ratio 3:2) 4-methylimidazole is reacted with sodium hydride, followed by 4-methane 4-(3,4 -Second gas - stupid -31 - This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 __'__B7 __ V. Inventions and explanations (28) Base) -1Η-Salt follow-up Treatment - After extraction and subsequent chromatography, the title compound free base was obtained, which was converted to its white hydrochloride. MS: m/e = 306 (M+). Example 7 Ιτί 一气-笑基)-1Η Miso-4·基甲一1-4.5,6.7-tetraki-1Η-benzimidazole, hydrochloric acid chisel 4,5,6,7-tetrahydrobenzimidazole is reacted with sodium hydride, followed by 4 曱 曱-Bu (3,4-dichloro-phenyl)-iH-imidation, subsequent treatment with extraction and chromatography to obtain the title compound free base, which was converted to its white hydrochloride. ;250 C (methanol / 乙趟), MS: m/e=346(M+). Example 8 1. Technique-_嗤'1-『『Bu (3,4-diazepine-based 丫-1 only-咄地-4- Methyl bromide 4.5-dimercapto-, guanidine hydrochloride < Ί · 9 Λ 4,5-dimethylimidazole and sodium hydride, followed by 4 曱 曱 丨 丨 丨 丨 二 二 苯基Subsequent treatment with 1 Η-imidazole, after extraction and subsequent chromatography, obtained the title compound as a free base, which was converted to white salt, m.p. <250 ° C (decyl alcohol / diethyl ether), MS: m/e =320(M+). Example 9 1H-flavored saliva '1-ΓΓΐ_ρ,4·dimercapto)_1H-imiphate_4_yl)methyl μ2_^ base-, sterol hydrochloride 9) 2-phenyl The imidazole is reacted with sodium hydride, followed by 4-sulfomethyl-1-(3,4-di-phenyl)-1 hydrazine-imidazole, followed by extraction and subsequent chromatography to obtain the title compound free base. It is converted to its white hydrochloride. Melting point 197-198 ° C (methanol / diethyl ether), MS: m / e = 369 (M + H +). • 32 - This paper scale applies to China National Standard (CNS) A4 specifications (210X 297 public) 1328584 A7 B7 V. Description of invention (29) Example 10 1H-ball+, 1-ΓΓ1-(4-oxomethyl-fundy)-1Η-啼一一甲1-Up·Λ篡-, citrate (1:21 Π-(4-gas-3-methyl-phenyl)-1Η·imidazol-4-yl]-nonanol was treated with sulfinium chloride 4-Chloromethyl-3-n-yl-styl)_ιη·smell is directly used in the reaction. '2-Ethyl imidazole was reacted with sodium hydride as described in Example 1, followed by subsequent treatment with 4-chloromethyl-1-(4· gas-3-methyl-benyl)-1Η-flavored salic acid hydrochloride. The title compound free assay was obtained after extraction and subsequent chromatography and was converted to its white hydrochloride. Melting point 186-187 ° C (methanol / diethyl ether), MS: m / e = 300 (M+). Examples 11 to 103 were prepared according to the schematic procedure described in Example 1〇. Example 11, 1-ΓΓ1-(4-lact-3-methylphenyl-yl)methyl Ί 2 甲 、, pound acid salt (1:2) [1-(4- gas-3-fluorenyl- Phenyl)-1Η-imidol-4-yl]-methanol was first treated with a helium gas, then treated with a reaction mixture of sodium hydride and 2-methyl-imidazole. After extraction followed by chromatography and chromatography, The title compound is in a free state. The free state is converted to its white hydrochloride salt. 218-220 ° C (methanol / ethyl bond), MS: m / e = 286 (M +). Example 12 1H-flavor啥, 1-(4-气-3-曱基笨基)-4-ΠΗ-咕 暮-1-暮-甲甚,焦酸盐(1:2) [1-(4-chloro-3-甲) Base-phenyl)-1Η-imidazol-4-yl]-methanol First use the sub-enzymes This paper scale applies to Chinese national standards (CNS>Α4 specifications (210X 297 mm) -33- 1328584 A7 B7

The gas treatment was then treated with a reaction mixture of sodium hydride and imidazole. After the subsequent treatment and chromatography, the title compound was obtained as a free state test. This free base is converted to its white hydrochloride. Melting point 206-207. (: (sterol/Byco) MS: m/e = 272 (M+). Example 13 1H-味峻' 1-丨丨1-(4-Ga-3-methylphenyl)-1H-alcohol -4-A 1 A, 4 i, dimethyl-, hydrochloride Π: 2) [1-(4-Ga-3-indolyl-phenyl)-1 Η-imidazol-4-yl]- Methanol was first treated with a helium-neutral treatment and then treated with a reaction mixture of sodium hydride and 4,5-dimercaptoimidazole. After the extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Hyun spot > 25 〇 (methanol / diethyl ether), MS: m / e = 300 (M +). Example 14 1-"1-(4-乱-3 -曱基笨基)-1Η - Mimi-4 -yl 1-4.5^(^7 - four-window.-1H-Pentimidazole-, hydrochloric acid Salt (1:2) [Bu (4) gas-3 -mercapto-phenyl)-lH-c-m--4-yl]-nonanol is first treated with agglomerated gas, then sodium nitride and 4,5 , 6,7 - four gas benzene and saliva anti-heptane mixture treatment. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Melting point > 250 ° C (nonanol/diethyl ether), MS: m/e = 326 (M+). Example 15 1H-Miso, chloro-3-methylindolyl)-1Η-am-4-one 1 A certain l-2-f thiopurine V, hydrochloride (1:2) Π-(4- Gas-3-methyl-phenyl)-1Η-啼吐-4-yl]-sterol First use 亚-醯-34- This paper scale applies to Chinese National Standard (CNS) Α4 specification (210X 297 mm) 1328584 A7 B7, then treated with sodium hydride and imidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point 214-2163⁄4 (furfuryl alcohol / diethyl ether), MS: m/e = 264 (M+). Example 19 1Η-_ sniffing ' 1-[Π_(3,4-methylphenyl)-lH-°米峰·4-11 A certain 1-2·Bis-, hydrochloride 0:2) [ 1-(3,4-Dimethyl-phenyl)-1Η-imidazol-4-yl]·methanol was first treated with sulfoximine gas and then treated with a reaction mixture of sodium hydride and 2-ethyl hydrazine. The title compound was obtained in a free state after extraction and subsequent chromatography. This free state was converted to its white hydrochloride. Melting point > 250 °c (sterol/accuracy), MS: m/e = 280 (M+). Example 20 1H-Miso '1-ΓΠ-(3,4-dimethyl phenyl ketone 4-yl 1 甲甲甲-, hydrochloride (1:2) [1-(3,4-di) Mercapto-phenyl)·1Η-imidazol-4-yl]-nonanol was first treated with sub-grinding chlorine' and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. The title compound was obtained as a free library. The free state was converted to its white hydrochloride. Melting point 249-25 (methanol / sigma), MS: m/e = 266 (M+). Example 21 1H-P /H 吐·, 1-(3,4-dimethyl stupid~)-4-(1Η-^Η 吐-1-基-甲某y, riding - S love salt (1:2) [1- (3,4-Dimercapto-phenyl)-1Η-imidazol-4-yl]-nonanol

This paper scale applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1328584 A7 B7

V. INSTRUCTIONS (33) ----- Gas treatment' is then treated with a reaction mixture of sodium hydride and imidazole. After the subsequent treatment and chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point 218_219eC (methanol / diethyl ether) MS: m / e = 252 (M+). Example 22 lEr 嘘 嘘 ; 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 甲基 _1 _1 _1 _1 _1 _1 , , , , , , , , , , , , , , , , , , , , 252(M+)»(1-p-Tolyl-1H-imidazol-4-yl)-nonanol was first treated with sulfinium chloride and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point > 25 (rc (sterol/diethyl ether), Ms: Example 23

(1-P-Phenylphenyl) 1Η·^_4·yl)-Methanol was first treated with a helium gas and then treated with a reaction mixture of sodium hydride and imidazole. to

m/e = 238 (M+). Example 24

Azole-4-one 1 methyl 1-2 methyl--, hydrochloride (1:2)

-37- _ This paper silver scale is applicable to China National Standard (CNS) A4 specification (2i〇X297 public love j '.----- 1328584 A7 B7 V. Invention 'Note (34) Chlorine treatment, then use sodium hydride And the reaction mixture of 2-methylimidazole is treated. After the subsequent treatment of the extraction and chromatography, the title compound is obtained as a free base. The free base is converted to white hydrochloride. m.p. 210-212. B.) MS: m/e = 270 (M+). Example 25 1H-imidazole, 2-ethyl-1-indole 1-(4-fluoro-3-methyl-methyl-V1H-imidazole-4- 1 base 1, hydrochloride (1:2) [1-(4-fluoro-3-indolyl-phenyl)-1 oxime-sodium-4-yl]-sterol is first treated with sub-branched chlorine. Then, it is treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After the subsequent treatment of extraction and chromatography, the title compound is obtained as a free state: the free state is converted to its white hydrochloride, melting point 210 -212 ° C (methanol / diethyl ether), MS: m / e = 284 (M + ). Example 26 1H-imidazole, 1-(4-fluoro-3-methyl-m-)-4-indole-carbazole-1 -yl-methyl)·, hair acid hydrazine: 2) [1-(4-fluoro-3-indolyl-phenyl)-1 fluorene-naphtho-4-yl]-methanol Stuffed gas treatment 'and then the reaction mixture is treated using sodium hydride and flavor of cushions. After the subsequent treatment and chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Mp 242-243 ° C (sterol/B domain), MS: m/e = 256 (M+). Example 27 1-H-Imidazole '2-Methyl-1-indole 1-(4-(methylthio), 1-1H-哚岫-4-, 1 methyl)-, hydrochloride (1 :2) [1-(4-Mercaptothio-phenyl)-iH-mio-4-yl]-sterol First use sub-items • 38· This paper is used in silver scales. CNS) A4 size (21〇χ297 mm)

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Line 1328584 A7 B7 V. Invention · Description (35) ;-- Brewing treatment' is then treated with a reaction mixture of sodium nitride and 2-methylimidazole. The title compound was obtained as a free base after extraction and subsequent chromatography. This free base is converted to its white hydrochloride. Hyun spot 242_243, c (methanol/diethyl ether), MS: m/e = 284 (M+). Example 28 1H-Mim sniff '2-B's gentleman's f (Methylthio-)^-based ι_Ί 呻< Ice-based 1 methyl V, hydrochloride (1:2) [1-(4·曱-sulfur The alkyl-phenyl)-m-miso-4·yl]-methanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After the extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its pale yellow hydrochloride. Melting point i 6 丨 丨 62 (sterol/ethyl ether), MS: m/e = 298 (M+). Example 29 1H-哞唆' 4-(1,ϋ-·生-卜棊-甲甲硫) Xiaomou^, Phenolate Π: 2) [1-(4(-fluoro-3-methyl-) Stupid)-1Η-β-sodium-4-yl)·sterol is first treated with chlorinated chlorinated chlorinated solution and then treated with a mixture of weathered and sulphur-like reaction mixture for subsequent treatment and chromatography. A free test. The free state was converted to its pale yellow hydrochloride salt 233-234 ° C (methanol / diethyl ether), MS: m / e = 270 (M +). Example 30 1H-imidazole, 2·甲棊_-ΗΠ·(3-(毛基)笑某ι·1Η_啐地其1 A certain V, pound acid salt (1:2) [1-(3-three Fluoromethyl-phenyl)-1Η-imidazol-4-yl]·methanol first using sulfinium-39-

This paper scale applies to the China National Standard (CNS) A4 specification (210X297 public Y

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Gas treatment was then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. The title compound was obtained in a free state after extraction and subsequent chromatography. This free state test was converted to its white hydrochloride. Melting point 218-220 (methanol / diethyl ether), MS: m/e = 306 (M+). Example 3 1 Xun Mi Tu's St. Ethyl-1-丨丨1-(3_(Trifluoromethane m-imiphate 1 fluorenyl V, pound acid salt (1:2) [1-(3- main fluorocarbon Base-phenyl)-1Η-imidazol-4-yl]·methanol was first treated with sulfoximine gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction followed by chromatography and chromatography, The title compound is in a free state. The free ill is converted to its white hydrochloride salt. mp 216-218. 〇 (methanol / ether), MS: m/e = 320 (M+). ' 4-(1 哞 哞 -1--1-yl-methyl trifluoromethyl, octagonal, hydrochloride (1:2) [1-(3-trifluoromethyl-phenyl)-1 Η-imidazole -4-yl]-sterol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and imidazole. After the subsequent treatment and chromatography, the title compound was freely tested. It was converted to its white hydrochloride. Refining point 224-226 ° C (methanol / sigma) MS: m / e = 292 (M +). Example 33 2.H-imida' 2-ethylfluoro-3- ( Trifluoromethyl) 竿 卜 1H miso _ 4-yl 1 methyl 1-, hydrochloride (1:2) [1-(4-fluoro-3-trifluoromethyl-phenyl)-1 Η- taste 4-yl] - ol Yue first used ethylene -40-

1328584 A7 _ B7 V. INSTRUCTIONS (37) Sulfur helium treatment, followed by treatment with a reaction mixture of sodium hydride and 2-ethylimidazole. The title compound was obtained as a free test after extraction and subsequent chromatography. This free state was converted to its pale yellow hydrochloride. Hyun spot > 238 ° C (decomposition) (methanol / diethyl ether), MS: m / e = 338 (M +). Example 34 1H-imidazole, fluoro.3_(trifluoromethyl)mosa 咄岫4. Its 1 methyl 1-2-methyl--hydrochloride (1:2) [1_(4-fluoro-3) -Trifluorodecyl-phenyl)-1Η-ylide-4-yl]-methanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After the subsequent treatment of extraction and chromatography, the title compound was obtained as a free test. This free state was converted to its pale yellow hydrochloride. Melting point > 23 1 °c decomposition (sterol/ethyl ether), MS: m/e = 324 (M+). Example 35 1Η-° rice saliva, 1-“4-fluoro-3-(trimethylmethyl)phenyl1-4-Π.Η-0 to peak-1-yl-methyl)-, hydrochloric acid test η: 2, [1-(4-ran-3-trifluoromethyl-phenyl)-1Η-sodium-4-yl]-methanol is first treated with sulfinium gas, then treated with a reaction mixture of sodium hydride and imidazole . The title compound was obtained in a free state after extraction and subsequent chromatography. This free state was converted to its pale yellow hydrochloride "melting point" > 246 ° C decomposition (sterol / diethyl ether), MS: m / e = 310 (M +). Example 36 1H-imidazole, 1-anthracene 3-fluoro-4-[trifluoromethyl)phenylidene 4-indole-carbazole-1-some·methyl)-, hydrochloride salt: 2) [1-( 3-Fluoro-4-trifluoromethyl-phenyl)-1 Η-bee pent-4-yl]-sterol First use of the Asian 41 - This paper scale applies to the Chinese National Standard (CNS) Α 4 specifications (210 X 297 mm)

Treatment with sulfonium chloride, followed by treatment with β sodium hydride and a reaction mixture of sodium methoxide, followed by extraction and subsequent chromatography to obtain the title compound in a free state. This free state test was converted to its pale yellow hydrochloride. Melting point 232-234 ° C (methanol / diethyl ether), MS: m / e = 311 (M+H+). Example 37 1H-Imidazole ' 1- Γ 1-Π-Fluorine_4-(Trifluoromethyl) Molybdenum i_m·carbazole _4-Ting] Methyl 1-2-methyl--, hydrochloride Π: 2 Π-(3-Fluoro-4-trifluoromethyl-phenyl)-1 oxime-salt-4-yl]-nonanol was first treated with sulfinium, followed by sodium hydride and 2-methylimidazole The reaction mixture is treated. After extraction and subsequent chromatography, the title compound was obtained as a free cancer test. The free cancer test was converted to its pale yellow hydrochloride. The melting point was 238-239 ° C (methanol / diethyl ether), MS: m/e = 325 (M+H+). Example 38 Taste, 2-ethylfluoro-4-(trifluoromethyl) acetonide _ 4-yl 1 methyl 1-, hydrochloride (1:2) [1-(3-fluoro-4- Trifluoromethyl-phenyl)-1Η-imidazol-4-yl]• decyl alcohol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction and subsequent chromatography, the title compound was obtained as a free ill test. The free cancer test was converted to its white hydrochloride. Hyun point 222-224 °C decomposition (sterol / ether), MS: m / e = 339 (M + H +) » Example 39 1 ϋ - imidazole, 2-methylformamidine-3- (three, fluorine stupid uH -咕嗦-4-yl 1 methyl 1·, hydrochloride (1:2) [1-(4-methyl-3-tris-methyl-phenyl)-1Η- miso-4-yl Methanol was first treated with -42- 1328584 A7 B7. The invention was treated with sulfinium gas, and then treated with a reaction mixture of sodium hydride and .2-mercaptopurine. After the subsequent treatment and chromatography, the title compound was obtained as a free state. The base is converted to its off-white hydrochloride. ·Soluble point > 235 ° C decomposition (sterol / ether), MS: m / e = 320 (M +). Example 40 m, 2 · B Base ri-""i-"U-based_3_(三荦甲篡)竿芊 1H-imidazol-4-yl 1methyl 1-, hydrochloride (1:2) [1-(4-fluorenyl) -3-Trifluoromethyl-phenyl)-1Η-°m-7-yl]-methanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethyl hydrazine. After the subsequent treatment and chromatography, the title compound was obtained in a free state. The free state was converted to its off-white hydrochloride. Melting point > 25 ° ° C (methanol / B) ), MS: m/e = 334 (M+). Example 41 jjj-mi saliva, 4-(1Η·. 吨-1-ylmethyl)-ΐ·“4·甲爷(一竹甲)芏Base 1-, Hydrochloric acid conversion: 2) [1-(4-Mercapto-3-trifluoromethyl-phenyl)-1Η-imidazol-4-yl]·nonanol was first treated with agitated chlorine. Treated with a reaction mixture of sodium hydride and imidazole. After the subsequent treatment of the extraction and chromatography, the title compound is obtained as a free base. The free base is converted to its pale white hydrochloride. Melting point > 25 (rc (sterol) / Ether), MS: m/e = 306 (M+) » Example 42 JJL-Mi啥' 1- "丨1-_(4-甲棊-3-甲氧甲甲幕)^ 2-Ethyl-, Carboxylate (1:2) [1-(4-Chloro-3-indole-stupyl)-1H.imidazole_4_yl sterol First use sulfinic acid paper scale applicable Chinese National Standard (CNS) A4 Specifications (210X297 public)

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Gas treatment followed by treatment with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its off-white hydrochloride. Melting point 244-246 ° C decomposition (methanol / ether), MS: m / e = 316 (M +) » Example 43 ten spray - ' 1- 『 [. 1- (4 · - methyl _3 · 曱 策 策))-IHd card s___ yl 1 methyl ι_ 2-methyl-, hydrochloride (1:2) [1-(4- gas-3-methoxy-phenyl)-1 Η-imidazole-4 The -methanol--methanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. The free base is converted to its off-white hydrochloride. Melting point > 25 〇 (methanol / diethyl ether), MS: m / e = 302 (M +). Example 44 1H Dimime' 1-(4-oxo-3-methoxyphenyl)-4-(1Η-咄咄-1竿-formamidine, decanoate (1:2) [1-(4 - gas-3-oxo-phenyl)-1Η-imidazol-4-yl]-nonanol is first treated with sulfinium chloride, then treated with a reaction mixture of sodium hydride and imidazole. Subsequent extraction and chromatography After that, the title compound was obtained in a free state. The free base was converted to white salt. m.p. 22 1-2221 (methanol / hexane) MS: m/e = 288 (M+). - leather 1 methyl 1H-imidazole, 2-ethyl-W "l-(4-翁.-3-篡1-, hydrochloride (1:2) [1-(4-oxo-3-oxo-) Stupid base)-1Η-味唾-4-yl]_sterol first use sulfinium-44- This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1328584 A7 B7 V. Description of invention ( 41) Gas treatment, and then treatment with a reaction mixture of sodium hydride and 2-ethyl flavonoids. After the subsequent treatment of extraction and chromatography, the title compound is obtained in a free state. The free state ruthenium is converted into its grayish white hydrochloric acid. Salt. Melting point >250 ec decomposition (sterol/diethyl ether), MS: m/e=300 (M+) » Example 46 _11~1-° rice spit, 1-『『1- (4-Fluoro-3-methyl-charged)-1幵-, sal-4-a 1-methyl1-2-methyl-, hydrochloride Π: 2)

[1-(4-Fluoro-3-methoxy-phenyl)-1Η-imidazol-4-yl]-nonanol was first treated with sulfoximine gas and then a reaction mixture of sodium hydride and 2-methylimidazole was used. deal with. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. The free base is converted to its off-white hydrochloride. Melting point >22〇»c decomposition (sterol/diethyl ether), MS: m/e = 286 (M+). Example 47 1H-pyrazine, 1-(4-fluoro-3-oxooxyphenyl)-4-indolyl-pyranyl-1-yl-methyl)-, pound acid salt (1:2)

[1-(4-Fluoro-3-indolyl-phenyl)-1Η-imidazo-4-yl]-nonanol was first treated with a helium-neutral treatment and then treated with a reaction mixture of sodium hydride and imidazole. After the subsequent treatment and chromatography, the title compound was obtained as a free assay. The free base is converted to its off-white hydrochloride. Melting point 174-178X: (methanol / diethyl ether), MS: m / e = 272 (M +) » Example 48 】 H-sweet, 1-丨丨 1-(4-气笨基)-1Η-imipen-4 -篡1甲甲甲早. Hydrochloric acid [1·(4-gas-stupyl)-1Η-imidazol-4-yl]·sterol first treated with sulfinium chloride 45 1328584 A7B7 V. Description of invention (and then used The reaction mixture of sodium hydride and 2-mercaptoimidazole is treated. After the subsequent treatment of extraction and chromatography, the title compound is obtained as a free base. The free state is converted into its pale yellow hydrochloride. Hyun Point 243-244 °C (methyl leaven / diethyl ether), MS: m/e = 272 (M+). Example 49 _lH-- azole, l-ffl.-(4-carbophenylmethylpyrazine 9·hexyl·, 1:2) [1-(4-Ga-phenyl)-1Η-imidazol-4-yl]·Methanol was first treated with sulfinium chloride. Then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. The free base was converted to white salt. m.p. 200-20 1. (: (sterol/s), MS: m/ e = 286 (M+). Example 50 1H-mip, 1-(4-gas-based)-4-ΠΗ-imida-1-one-methyl v, hydrochloric acid Salt Π: 2) [1-(4-Ga-phenyl)-1Η-imidazol-4-yl]-methanol is first treated with sulfinium gas, then treated with a reaction mixture of sodium hydride and imidazole. After treatment and chromatography, the title compound was obtained as a free base. The free base was converted to white salt. mp 228-229 ° C (methanol / EtOAc), MS: m/e = 258 (M+ Example 51 1H-Sneeze, 1-ΓΓ1-Π.3-笑#Diargon-5-yl)-1 H-味峰·4·1 methyl1-2-ethyl-, salt Acid salt (1:2) (1-Bute and [1,3] Dioxin-5-yl-1Η-Miso-4-yl)-sterol first use sub-46- This paper scale applies to China Standard (CNS) A4 specification (210X297 mm)

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k. 1328584 V. Description of invention (A7 B7

The mixture is treated with sulfonium and then treated with a reaction mixture of sodium hydride and 2·ethylimidazole. The title compound was obtained as a free test after extraction and subsequent chromatography. This free state was converted to its white hydrochloride. Hyun Point >25〇«>c (Methanol/Byco), MS: m/e=296 (M+). Example 52 1Η-°米 sniffing, 1-Γ『1-Π,3-Benzo 2 gas 囿-5-棊) Pei -4- a certain methyl 1-2-A--, pound salt Π :2) (1-Benzo[1,3]dioxoindol-5-1H-imidin-4-yl)·sterol is first treated with arsenic helium and then using sodium hydride and 2-methylimidazole The reaction mixture is treated. The title compound was obtained as a free base after extraction and subsequent chromatography. This free base is converted to its white hydrochloride. Melting point > 25 〇〇C (methanol / diethyl ether), MS: m/e = 282 (M+). Example 53 1Η-°米唾' 1-(1,3-Anodic dioxin-5-something ton-1_some_甲)-, hydrochloride (1:2) (1-this [1,3]-oxosulfonium-5-1Η-°m唆-4-yl)-sterol was first treated with a sub-grinding gas and then treated with a reaction mixture of sodium hydride and imidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Hyun point 197_198. 〇 (methanol / diethyl ether), MS: m/e = 268 (M+). Example 54 _ljj-mimi, 1-|~[1-(3-fluoro-4-H phenyl carbazide-4-yl 1 ketyl: > _ methyl-, hydrochloride (1:2) [1-(3-Fluoro-4-indolyl-phenyl)-1Η-imidazol-4-yl]-nonanol First use sulfinium-47- This paper scale applies to China National Standard (CNS) Α4 specification ( 210 X 297 mm) 1328584 A7 _B7 V. Description of the invention (44~'-a gas treatment' and then treated with a reaction mixture of sodium hydride and 2-mercapto-bite. After the extraction and chromatography, the title was obtained. The compound is in the form of a free base. The free base is converted to its white hydrochloride. Melting point > 250 ° C (decyl alcohol / diethyl ether), MS: m/e = 270 (M+). Example 55 j_H-M. , 2_ethyl-lf "l-(3-fluoro_4·甲盖苹早viH-imidazol-4-yl·[methyl 1-, hydrochloride (1:2) [1-(3-fluoro -4-Methyl-phenyl)-1Η-imidazol-4-yl]-nonanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After the analysis, the title compound was obtained in a free state. The free state was converted to its white hydrochloride. The melting point > 25 〇. 匚 (methanol / diethyl ether), MS : m/e = 284 (M+). Example 56 j_H-Mimi. Sit ' 1-(3-Fluoro-4-methylphenyl)-4-(1 -°米啥-1-yl-甲某v , sleep • acid salt (1:2) [1-(3-fluoro-4-mercapto-phenyl)-1Η-imidazol-4-yl]-methanol was first treated with sulfinium, then sodium hydride and The reaction mixture of imidazole is treated. After the subsequent treatment and chromatography, the title compound is obtained as a free base. The free state is converted to its white hydrochloride. The melting point is 223-224 ° C (sterol / acetyl MS: m/e = 256 (M+). Example 57 1H - miso' 1-"|~1-(3-gas-4-曱氡 某某味峡-4 yl 1 methyl ι·2· Methyl-, hydrochloride (1:2) [1-(3- gas-4-oxo-phenyl)-1Η-imidazol-4-yl]-sterol First use sulfinamide sleep 48-paper The music scale applies to the Chinese National Standard (CNS) Α4 specification (210 X 297 mm) 1328584

The gas treatment was then treated with a reaction mixture of sodium hydride and 2-methylimidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Melting point 240-241 eC (sterol/ethyl bond), MS: m/e = 302 (M+). Example 58 1 good · Mimi saliva ' 1- 『 1- (3- gas 4-曱 oxy methoxy) saliva-4- a 1 A certain 1-2_ ethyl-, hydrochloride (1:2) [ 1-(3-Ga-4-oxo-phenyl)-1Η-imidazol-4-yl]·nonanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. The title compound was obtained in a free state after extraction and subsequent chromatography. This free state was converted to its pale yellow hydrochloride. Melting point 220-22 leC (methanol/diethyl ether), MS: m/e = 316 (M+). Example 59 ΙΗ- 吐 吐 ' l-(j-Ga-4-indoxy phenyl-1-yl-methyl, hydrochloride (1:2) [1-(3- gas-4-methoxy- Styrene)-1Η-imidazol-4-yl]-nonanol is first treated with sulfinium chloride and then treated with a reaction mixture of sodium hydride and imidazole. After extraction followed by chromatography and chromatography, the title compound is obtained as free state. The free base is converted to its white hydrochloride salt. mp 245-246 ° C (decanol/diethyl ether), MS: m/e = 288 (M+). Example 60 1H-imidazole, 1-indole -(4-Ga-2-fluoroindolyl Viff-oxazol-4-ylmethylbu- 2-methyl--, pound acid salt (1:2) [1-(4-Ga-2-fluoro-phenyl) )-1Η-imidazole-4·yl]-sterol first use sulfinamide-49. This paper scale applies to China National Standard (CNS) A4 specification (210x 297 mm)

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k 1328584 Five invention description ( 46 A7 B7

Treated and then treated with a reaction mixture of sodium hydride and 2-methyl oxazole. After extraction and subsequent chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point 235_236 charged (sterol/acetamidine), MS: m/e = 290 (M+). Example 61 i_H-spider spray, 1-ΓΠ-(4-chloro-2-fluoromethane _4-yl 1 methyl 1-2-fluorenyl-, hydrochloride hydrazine: 2) [1-(4- Gas-2-fluoro-phenyl)-1Η-imidazol-4-yl]-nonanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free base is converted to its white hydrochloride. Melting point 248_249»c (methanol / y), MS: m/e = 304 (M+). Example 62 1H-imidazole, 1-(4-Ga-2-fluorophenyl V4-(1H-carbazole-1-m-methyl)·, sleeping cabin salt (1:2) [1-(4-gas -2-Fluoro-phenyl)-1 oxime-salt-4-yl]-nonanol was first treated with agglomerated gas, then treated with a mixture of sodium hydride and hydrazine. After extraction followed by chromatography and chromatography The title compound is obtained in a free state. The free base is converted to its white hydrochloride salt. Melting point > 212 ° C decomposition (methanol / B), MS: m/e = 276 (M+). Example 63 1H -Imidazole, 1-ΓΓ1-Μ-bromo-V1H-咄咄-4-yl 1 formazan 1-2- 7. + _ hydrochloride (1:2) [1-(4-bromo-phenyl)- 1Η-imidazol-4-yl]-nonanol is first treated with sulfinium chloride -50 - This paper scale applies to the S national standard (CNS> A4 specification (210X297 public) 1328584 A7 B7

5. Description of the invention (47, then treated with sodium hydride and 2-ethylimidazole. The reaction mixture was subjected to subsequent treatment and chromatography to obtain the title compound as a free base. The free base was converted to white. Hydrochloride. Melting point > 250 ° C (methanol / ethyl acetate), MS: m/e = 330 (M+). Example 64 1H-mpy, 1-ΓΠ·(4-bromophenyl)-1Η-啥-4- certain 1 methyl 1-2-methyl-, hydrochloride (1:2) [1-(4-di-phenyl)-1Η-miso-4-yl]-methanol first used sub Continued aeration treatment and then treated with a reaction mixture of sodium hydride and 2-methyl 0 m saliva. After the extraction and subsequent chromatography, the title compound was obtained as a free base. The free base was converted to its white salt. Acid salt. Melting point > 25 0. (: (sterol / acetamidine), MS: m / e = 316 (M +). Example 65 111-flavor. Sit 'odor phenyl) -4- (lH-g Tons-1-yl-methyl)-, hydrochloride continued (1:2) [1-(4-bromo-phenyl)-1Η-imidazol-4-yl]-methanol was first treated with sulfoximine gas and then used Treatment of the reaction mixture of sodium hydride and 2-ethylimidazole. After the extraction and subsequent chromatography, the title compound was obtained. In a free state, the free base is converted to its white hydrochloride salt. Melting point 23 7-23 9. (: (decyl alcohol / diethyl ether), MS: m/e = 302 (M+). Example 66 1H-imidazole ' 1-『『1-(4-Difluorodecyloxy) mosyl μ1Η-carbazol-4-yl 1methyl1-2- Λ&-, hydrochloride (1:2) [1-(4- Difluoroanthracene-phenyl)-1Η-imidazol-4-yl]-nonanol was first used with sulfinamide-51 - This paper size is applicable to the Medium Standard (CNS) Α4 specification (210 X 297 mm) 1328584 A7 B7

The chlorine treatment was awake&apos; and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction and subsequent chromatography, the title compound was obtained as a free cancer test. This free state test was converted to its white hydrochloride. Hyun ^ point 232-235 (methanol / B bond), MS: m / e = 282 (M +). Example 73 1H-Imidazole, 4-(1Η-imidazol-1-yl-methylhydrazine): h(3-methylhydro_4_甲茇茇)... Hydrochloride Π: 2) [1-(3-曱Oxy-4-methyl-phenyl)-1Η-imidazol-4-yl]-nonanol was first treated with a sulfene aerated treatment and then treated with a reaction mixture of sodium hydride and imidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its pale yellow hydrochloride. Hyun point 249-251 ° C (methanol / puzzle), MS: m / e = 268 (M +). Example 74] JH-imidazole' 2_-ethyl-1-indole 1-indole 4-(trifluoromethyl)methane 丨·丨η-imidazole _4_ 11 曱yl 1-, hydrochloride (1 :2) [1-(4-Trifluoromethyl-phenyl)-1Η-imidazo-4-yl]-methanol was first treated with a sub-continuous gas stream' followed by a reaction mixture of sodium hydride and 2-ethylimidazole deal with. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Hyun spot 240-242 ° C (methanol / diethyl ether), MS: m / e = 320 (M +). Example 75 1M-imidazole, 2-mercapto-l-["l-"4-trifluoromethyl methoxyl 1-1H-imidazol-4-indole 1 fluorenyl, </ RTI> (1:2) [ 1-(4·Trifluoromethyl-phenyl)-1Η-imidazol-4-yl]-methanol first using sulfinium-54-

1328584 V. Description of the invention (51 gas treatment, followed by treatment with a reaction mixture of sodium hydride and 2-mercaptocarazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. It is white hydrochloride. Melting point 246_248t (methanol / sigma), MS: m/e = 306 (M+). Example 76 UL- 一一唾 '味味素棊-棊-甲华)-144_(Trifluoro A, Xiaoxiao^ Hydrochloride (1:2) [1-(4-Trifluoromethyl-phenyl)-ih-imidazol-4-yl]-sterol is first treated with sulfinium gas and then used The reaction mixture of sodium hydride and imidazole is treated. After the extraction and subsequent chromatography, the title compound is obtained as a free base. The free state is converted to its white hydrochloride. Hyun point 220-222 ° C (methanol / B key) MS: m/e=292(M+). Example 77 .1_Η-咪嗤' 1-[丨1-(1,3-dihydro-5-iso-stuppy 咭uH_哚崦_4 _ its] thiol 1-2-ethyl-'hydrochloride: 2) [1-(1,3-isobenzopyrene 0^-5-yl)-1Η-0m啥-4-yl] - decyl alcohol is first treated with sulfoximine gas and then treated with a reaction mixture of sodium hydride and 2 · ethyl imidazole. After treatment and chromatography, the title compound was obtained in a free state. The free state was converted to its off-white hydrochloride. The melting point &gt; I 〇 8 ° C decomposition (sterol / ether), MS: m / e =294(M+). Example 78 jg-flavoring '1·"[·1_Π·3-diiso-p- and pyridyl 4-imidazolyl-4-yl 1 f-based 1-2-methyl-, hydrochloride π: 2) [1-(1,3-Igly-isobenzo-bito-5-yl)-1Η-imidol-4-yl]-methanol first makes -55- 1328584 A7 ___B7_ V. Description of invention (52) Treated with sulfinium helium, then treated with a reaction mixture of sodium hydride and 2-methylimidazole. After extraction and subsequent chromatography, the title compound is obtained in a free state. The free base is converted to its off-white salt. Acid salt. Melting point &gt; 250 ° C (methanol / diethyl ether), MS: m / e = 280 (M + ). Example 79 1H-imidazole, 1-indole-fluorene-fluoro-4-methyl-l-yl)-1Η -Mimi-4-yl 1A 1-2-A-, bismuth citrate (1:2) [1-(3-Fluoro-4-methoxy-phenyl)-1 Η-imidazol-4-yl ]-Methanol was first treated with sulfinium gas, then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction followed by chromatography and chromatography, the title was obtained. The free-form base is converted to its white hydrochloride salt, m.p. 23-240 ° C (decanol/ethyl ether), MS: m/e = 286 (M+). Example 80 1H-flavor Bite, 2-ethyl-1-indole-(3-fluoro-4-methoxy bromide)-1Η-°米嗤-4-一一甲一1-, pound acid salt (1:2) [1- (3-Fluoro-4-indolyl-phenyl)-1 Η-°m嗤-4-yl]-methanol was first treated with a sub-continuous gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point 218-220 ° C (sterol / B _), MS: m / e = 300 (M +). Example 81 1H-wortazole, ΐ4Π-(4-oxime-oxymethyl V1H-imidazole-4·1 methyl1-2·A$-, hydrochloride (1:2) [1-(4-oxo) - Stupid base -1Η·imidazol-4-yl]-sterol first use sulfinium chloride -56- This paper scale applies to China National Standard (CNS) Α4 specification (210 X 297 mm) 1328584 A7 ___B7 Description of the invention (53) </ RTI> then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained in a free state. The free state was converted to white. Hydrochloride. Melting point &gt; 250. 〇 (sterol / sigma), MS: m / e = 268 (M +). Example 82 1H - 嗤 ' 2-3 碁 two (?: A pen base) _1H•咄衅基·!甲μμ, hydrochloride (1:2) [1-(3·methoxy-phenyl)-1Η-imidazol-4-yl]-sterol was first treated with sulfinium 'There was then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After the extraction and subsequent chromatography, the title compound was obtained in a free state. The free sorrow was converted to its white hydrochloride. -248 ° C (methanol / diethyl ether), MS: m / e = 282 (M +). Example 83 1 Η - _ spit, l-LH- (3-(3-oxo-phenyl)-1Η·哔 eat_4-一一曱I-2-methyl·, hydrochloride (1:2) [1-(3-曱-oxy-phenyl) -1Η-imidazol-4-yl]•sterol was first treated with sulfinium chloride. Then it was treated with sodium hydride and 2-mercapto. The reaction mixture was extracted. After extraction and subsequent chromatography, the title compound was obtained. The free state was converted to its white hydrochloride. H.S. 242-243 ° C (methanol / ether), MS: m/e = 268 (M+). Example 84 1H-imidazole 4 -(ljj-imidazol-1-yl-methyl methoxy race, salt (1:2) [1-(3-methoxy-benyl)-1Η-miso-4-yl]-formaldehyde first used Continued Brewing Chlorine-57· This paper scale applies Chinese National Standard (CNS) A4 Specification (210 X 297 mm) 1328584 A7 _ B7 V. Invention Description (54~) &quot; Rational, then use sodium hydride and imidazole The mixture is treated. After the subsequent treatment of the extraction and the chromatography, the title compound is obtained as a free base. The free base is converted to the white salt. mp 219-220 ° C (decyl alcohol / diethyl ether), MS: m/e = 254 (M+). Example 85 1H-imidazole, 1-ΓΓ1-Γ4-methylindole-3-(trifluoromethyl)methyl MH-咄-4-篡1 methyl1-2-methyl-, pound acid salt (1:2) [1-(4-oxo-3-trifluoromethyl-phenyl)-1Η-imidazol-4-yl The sterol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. The free base is converted to its light brown hydrochloride. Melting point &gt; 222 ° C Decomposition (methanol / diethyl ether), MS: m / e = 337 (M + H +). Example 86 _1H-flavored saliva, 2·ethyl-l-ffl-f4·decyloxy-3-(trimethylmethyl)phenyl~|·ΐΗ-ρ-myzol-4-yl 1methyl 1-, salt Acid salt (1:2) [1-(4-Methoxy-3-trifluoromethyl-phenyl)-1Η-°m-ol-4-yl]-methanol was first treated with sulfinium gas and then hydrogenated. The reaction mixture of sodium and 2-ethylimidazole is treated. After extraction and subsequent chromatography, the title compound was obtained as a free test. This free state was converted to its light brown hydrochloride. Melting point &gt; 226 ° C decomposition (sterol / diethyl ether), MS: m / e = 351 (M + H +). Example 87 azole, 1-[Γ1-(3-氪-4-methylphenyl)-methyl-1,- decanoate (1:2) [1·(3- gas-4-mercapto-phenyl )-1Η-imidazole-4-ylbupropanethanol First use sulfinium-58- This paper scale applies to the Chinese Standard (CNS) A4 specification (210X297 mm) A7 B7

1328584 V. Description of the invention (55 chlorine treatment 'then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After the subsequent treatment of extraction and chromatography, the title compound was obtained in a free state. The free state was converted into Its white hydrochloride. melting point 242-243 ° C (methanol / sigma), MS: m / e = 286 (M +). Example 88 1H-weijun, gas-4-曱 a stupid base)·ιη· ρ朵-4-yl 1 A certain ι·9 _ ethyl-, hydrochloride (1:2) [1-(3-chloro-4-indolyl-phenyl)-1Η-imidazol-4-yl] - The sterol is first treated with sulfinium chloride and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. The title compound was obtained in a free state after extraction and subsequent chromatography. This free state test was converted to its white hydrochloride. Melting point 178-179 ° C (methanol / diethyl ether), MS: m / e = 300 (M+). Example 89 1H-啥啥' 1-(~Γ1-(3 -Ga-4-methylphenyl)-4-(1!^-°米唾-1-某-甲)·, hydrochloride ( 1:2) [1-(3-Chloro-4-indolyl-phenyl)-1Η-imisin-4-yl]-methanol was first treated with a sub-neuterium gas and then treated with a reaction mixture of sodium hydride and imidazole After the extraction and subsequent chromatography, the title compound was obtained as a free base. The free state was converted to white hydrochloride. mp 218-220 ° C (decanol/diethyl ether), MS: m/e =272(M+). Example 90 1H-imidazole, 『『1-Γ4-gas-3-(trifluoromethane) 笑一1-1H-imidazole-4-one 1 methyl1-2-methyl- , hydrochloride (1:2) [1-(4-chloro-3-trifluoromethyl-phenyl)-1Η·imidazol-4-yl]-sterol first used in sub-59- paper scale China National Standard (CNS) A4 specification (210X 297 public)

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1328584 A7 _____B7 V. INSTRUCTIONS (56) Treatment with chlorine, followed by treatment with a mixture of sodium hydride and 2-ethyl sulphate. After extraction followed by chromatography and chromatography, the title compound was obtained as a free base. This free state was converted to its white hydrochloride. Melting point 179-180. 〇 (sterol/B domain), MS: m/e = 354 (M+). Example 91 I_H-imidazole, 1-ΓΓ1-Γ4-gas-3-(trifluoromethyl, cage ΐ·1Η-咄咄-4-fur 1 methyl b-2-carboindole-, trans-acid salt Π: 2) [1-(4-Chloro-3-trifluoromethyl-phenyl)-1 oxime-sodium-4-yl]-sterol is first treated with sulphate, then sodium hydride and 2-methyl The saliva reaction mixture is treated. After the subsequent treatment of extraction and chromatography, the title compound was obtained as a free test. This free state was converted to its white hydrochloride. Melting point &gt; 250 ° C (methanol/diethyl ether), MS: m/e = 340 (M+). Example 92 LH-imidazole, 1-indole 4-gas-3-(trifluoromethyl) dish 1-4-anthracene-imidazole-1-methanone··, pound bismuth.-2)-gas-3 -Trifluoromethyl-phenyl)-1 oxime-imidazo-4-yl]-nonanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and imidazole. After extraction and subsequent chromatography, the title compound was obtained as a free base. This free base is converted to its white hydrochloride. Melting point &gt; 250 ° C (methanol / sigma), MS: m/e = 326 (M+). Example 93 1H-imidazole, 1-ΓΓΜ3·gas-4-fluoromethane V1H-carbazole-4-ylformamidine1·:&gt;·methyl-, guanidine hydrochloride: 2) [1-(3-gas -4-Fluoro-phenyl)-1Η-imidazol-4-yl]-methanol First use sulfinamide-60· This paper scale applies to China National Standard (CNS) Α4 specification (210X 297 mm) !328584

V. Description of the invention (57 A7 B7

Treated and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. After extraction and subsequent chromatography, the title compound was obtained as a free state. This free state was converted to its white hydrochloride. Hyun Point 224-225 (methanol / diethyl ether), MS: m/e = 290 (M+). Example 94 JH-Ball biting, 1-ΓΓ1-Π-chloro-4-fluoromethyl)-ιη·味味_4_基甲里-,mm salt (1:2) [1-(3-气-4 -Fluoro-phenyl)-1Η-imidazol-4-yl]-methanol was first treated with a sub-continuous gas and then treated with a reaction mixture of sodium hydride and 2-ethylimidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free state was converted to its white hydrochloride. Hyun point 248-2503⁄4 (methanol / ethyl), MS: m / e = 304 (M +). Example 95 1H-Imidazoline Salt: 2) 1-(3-Ga-4-fluorophenyl)-4-indole-Arachnene-丨-[1-(3-Ga-4-fluoro-stupyl) -1Η-imidazol-4-yl]-methanol was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and imidazole. After extraction and subsequent chromatography, the title compound was obtained in a free state. This free base is converted to its white hydrochloride. Melting point 2 10-212 ° C (furfuryl alcohol / ethyl ester) MS: m/e = 276 (M+). Example 96 1H-味吐' 1-"(1-『1,1'-联笨1-4-yl)-1Η-味峻-4-竿1甲^ γ-based, hydrochloride (1:2 ) (1-Biphenyl-4-yl-1Η-imidazol-4-yl)-nonanol was first treated with sulfinium, -61 -

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1328584 A7 ____B7 V. INSTRUCTIONS (58~) :-- Then treated with a mixture of sodium hydride and 2·ethylimidazole. The title compound was subjected to a free assay after extraction and subsequent chromatography. This free base is converted to its white hydrochloride. Melting point 248-253 eC (nonanol/ethylidene) MS: m/e = 328 (M+). Example 97 jjj-imidazole, dip-oxime 1.1'- phenylidene 1-4-yl-1H-oxazol-4. Methyl-, hydrochloride Π: 2) (1-biphenyl-4-yl-1Η-imidazol-4-yl)-nonanol was first treated with sulfinium chloride, then sodium hydride and 2-methylimidazole were used. The reaction mixture is treated. After the extraction and subsequent chromatography, the title compound was obtained as a free state. The free state was converted to its pale yellow hydrochloride. Melting point 169-175. (:(methanol/ethyl bond) MS: m/e=314(M+) » Example 98 jjj-mimi' 2-ethyl-1-ΓΓ1-Π-methyl-4-nf-based y, y 啼— oxazol-4-yl 1 methyl 1-, hydrochloride (1:2) [1-(4-isopropyl-3-methyl-phenyl)-111-°糸--4-yl]- Methanol was first treated with sulfinium chloride and then treated with sodium hydride and 2-ethylimidazole. After the subsequent treatment and chromatography, the title compound was tested in a free state. Conversion to its white hydrochloride. Refining point &gt; 1 8 〇 decomposition (methanol / diethyl ether), MS: m / e = 308 (M +). Example 99 1H - sodium saliva, 2-methyl-1-ΓΓ 1-Γ3 -Methyl-4-(1-methyl-[, 笑 ιιι Η 味 -4- -4- 1 某 某 某 某 某 某 转 转 转 转 2 2 2 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- Phenyl)-1 oxime-sodium-4-yl]-methanol first used sub-62- This paper scale applies China National Standard (CNS) Α4 specification (210χ297 mm) 1328584 A7 ____ B7 V. Invention description (59 The helium gas treatment is continued, and then treated with a reaction mixture of sodium hydride and 2-methylimidazole. After the subsequent treatment of extraction and chromatography, the title compound is obtained in a free state. The test was converted to its white hydrochloride. Melting point &gt; 25 〇 °c (sterol/ethyl scale), MS: m/e = 294 (M+). Example 100 1_Η-咪唾' 2-甲皋_- 1-『『ΐ·(4·Nitromethyl ViH-咣咄-4-yl 1methyl 1-, Hydrochloric acid conversion: 2Ί 1-(4-nitrophenyl)-1Η-imidazole-4-曱Alcohol (prepared according to ι· Antonini et al., synthesis, 1% 3, L 47_49) was first treated with a sulphur gas and then treated with a reaction mixture of sodium hydride and 2-methylimidazole. After the title compound was obtained as a free base, the free base was converted to its yellow hydrochloride. mp. &lt; 250. (: (methanol / ethyl ether), MS: m/e = 283 (M+). Example 101 j_H -°米唾' 2-乙革二1•“Nitrobenzimidazole_4yl]indenyl^, hydrochloride (1:2) 1-(4-nitrophenyl)-1Η-imidazole-4 - sterol (prepared according to L Ant〇nini et al., Synthesis, 1983, L 47-49) was first treated with sulfinium gas and then treated with a mixture of sodium hydride and 2-ethyl saponin. After chromatography, the title compound was obtained as a free base. The free base was converted to yellow. The salt of the salt. (M).肄-63 hydrochloride · This paper scale is suitable for g S material (CNS) ^ ^ grid (21GX297 public) --- 1328584 A7 B7 V. Description of invention (60 ) am 1-(4-nitrophenyl) _1H-Imidazole·4-methanol (prepared according to I. Antonini et al. 'Synthesis' 1983, L 47-49) was first treated with sulfinium gas and then treated with a reaction mixture of sodium hydride and imidazole. After the extraction subsequent treatment and chromatography, the title compound was obtained as a free base. The free base was converted to its yellow hydrochloride. Mp 245-246 ° C (decyl alcohol / diethyl ether), MS: m / e = 269 (M+). Example 103 M. 01 ' 1-(3.4-diphenyl)-5-methyl·4-indol-2-methyl-1H-imidazol-1-yl)indolyl 1-, hydrochloride 瞜η-?) [1- (3,4-diqi-phenyl)_5_mercapto-1Η-mi. Sodium-4-yl]-methanol was first treated with a prior art brewing gas and then treated with a reaction mixture of sodium hydride and 2-mercaptoimidazole. The title compound was obtained as a free test after extraction and subsequent chromatography. This free state was converted to its white hydrochloride. Melting point &gt; 24 〇 » 〇 解 solution (sterol / diethyl ether), MS: m / e = 320 (M +). Example 104 i-fl-(3,4-dioxa-benzoquinone)-ih-imidazole_4_yl-methyl ι·1Η·carbazole·2·ylamine-, sterol hydrochloride·?.) 1Η- Imidazole, W1-(3,4_digas_phenyl)_1Η_imidazole_4•ylindenyl]·2nitro-(2_1 g, 6.2 mmol) dissolved in acetic acid (50 ml), iron powder added (3 5 g, 62 mmol), and the resulting mixture was stirred at 6 ° C for 2 hours. After the addition of ethyl acetate (200 mL), the hot mixture was adjusted again to reflux and filtered. The entire volatiles were removed in vacuo and the residual acid was removed by distillation. The obtained semi-solid was purified by chromatography (purine, eluted with gradient dioxane to 1% by weight (dichlorodecane/methanol/aqueous ammonium hydroxide = 90:10:1) to obtain the title. 64-

1328584

The free base of the compound (1.9 g, ι 〇 0%), J-sub-white solid separation was treated with hydrochloric acid in decyl alcohol solution, and the title compound was isolated as a white crystalline solid. Melting point 164_165. C (methanol / diethyl ether), MS. m / e = 308 (M+H+). Examples 105 through 107 were prepared according to the general procedure described in Example 1-4. Example 105 Oxygen _3_ formazan-benzoquinone-methyl 呻-呻 beer_2·an amine-, sterol hydrochloride: 2) 1 Η-imidazole, 1-[1-(4-gas-3-methyl stupid The imidazole is reacted with iron in acetic acid. After filtration, the free base of the title compound is isolated by evaporation and chromatography. The free base is converted to white salt. 233 ° C (sterol / ethyl bond), MS: m / e = 288 (M + H +). Example 106 1-(1-p-tolyl-1H-imidazol-4-yl-methyl)-^-imidazole -2- its-amine ... (1:2) 1H-imidazole ' l-[[l-(4-mercaptophenyl)-1Η-imidazol-4-yl-methyl]_2-nitro and The iron is reacted with acetic acid. After filtration, the free base of the title compound is isolated by evaporation and chromatography. The free base is converted to white salt. mp 232-2331 (; decyl alcohol / diethyl ether), MS: m/e =253(M+) » Example 107 1-Π-茉-1H-indazol-4-yl-indenyl V1H-carbazol-2-yl-amine-, 豳 瞄 _ —— (1:2) 1H - Flavor spray, 2-nitro stupidyl ol-4-yl)-methyl]_ is reacted with iron in acetic acid. After filtration, the title compound is separated by evaporation and chromatography -65 - This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm)

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1328584 A7 B7 V. Description of invention (62) From the test. The free base is converted to its white hydrochloride. Melting point 153_155 ° C (sterol / diethyl ether), MS: m / e = 239 (M +) » Example 108 jiiA ^ __Ll_- "Π - (3, 4- two gas stupid VlH-咭咄-d its - A L-2.5-Dimethyl, hydrochloric acid sleep-[1-(3,4·dichloro-phenyl)-ιη·imidazol-4-yl·indenyl]•thioethylamine (0.60 g '2.0 mmol The suspension of acetone (1 ml) was treated with potassium carbonate (28 g, 2,0 mmol) and iodonane (0-26 g, 1.8 mmol). The mixture was refluxed for 1 hour to evaporate and suspend. In ethanol (3 ml), add propargylamine (1 g, 2 mmol) and reflux for 9 hours. After filtration and evaporation, the residue was purified by chromatography [Shi Xi Yao] with gradient dimethane to 30 〇 / 〇 (di-gas methane / methanol / aqueous argon arsenide = 90:10:1) elution], the free base of the title compound (2 g, 28%) was isolated as a light brown oil. Treatment with decyl alcohol solution followed by the addition of diethyl ether. The title compound was isolated as a white crystalline material, spurred &lt;25 〇〇C (methanol/diethyl ether), MS: m/e = 321 (M+H+). (3,4-di-phenyl-phenyl, 1-imidazol-4-yl-methyl-1-1-1-imidazol-2-even 1-nonanol 1-[1-( 3,4-Dioxo-phenyl)_11^imidazole-4-yl-indenyl]-111-imidazol-2-carbaldehyde (0.52 g, 1.6 mmol) in decyl alcohol (16 mL) Treated with sodium (0.12 g, 3.2 mmol). The mixture was stirred at room temperature for 2 hr. then the residue was evaporated and the residue was partitioned (ethyl acetate/water). The title compound was obtained as a white crystalline material (0.21 g, 41%). mp.

1328584 A7 ______ B7 V. Description of invention (63) m/e = 322 (M+). Example 110 N - {1 -1~ 1 - chaotic-name base) -1 Η-ρ 咬-4-基-甲 某 - - - - - - 1-[1-(3,4-dichloro-phenyl) a solution of 1-exidazolyl-4-yl-methyl]-111-imidazol-2-ylamine (1.0 g, 3.2 mmol) in THF (32 mL) using triethylamine at room temperature 33 g '3.2 mils) and acetochlor chloride (〇·25 g, 3.2 mM). The mixture was stirred at room temperature for 2 hours, and the organic phase was evaporated to dryness "chromatography [gelatin, with gradient dioxane to 50 〇 / 〇 (dioxane / methanol / aqueous ammonium hydroxide = 90: After 10:1) elution, the title compound (019 g, 17%) Melting point &gt; 236 ° C decomposition (ethyl acetate), MS: m/e = 350 (M+H+). Example 111 _{l-"l-(3,4-dioxa-based ViH-imidazol-4-yl-methyl 1-1 imidazole-2-one 1-ethyl-amine, hydrochloride (1: 2) 1^-{1-[1-(3,4-Di-(phenyl)phenyl)-1-imidazol-4-yl-methyl]-1!1-imidazol-2-yl}-acetamide (0.30 The mixture was treated with 1 M BH3 THF (1.6 mL) and refluxed for 2 hr. The mixture was cooled to 5. 〇, decyl alcohol (5 mL The mixture was extracted with EtOAc (3 mL) EtOAc. The title compound was obtained as a free base by chromatography. Treated with hydrochloric acid in decyl alcohol solution followed by diethyl ether-67- This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1328584

Thereafter, the title compound was isolated as an off-white crystalline material (yield: 62 g, 22%). Melting point &gt; 250 ° C (methanol / diethyl ether), ms: m / e = 336 (M + H +). Example 112 Dioxo-benzoquinone)-1-(2-methyl- 咄咄-^-yl-methyl oxime, oxalate Π: Π 1-(3,4-di-phenyl)·3·fluorenyl · 1 Η _ pyrazole (14 g, 6 "mole) in a solution of four gasified carbon with bismuth-bromobutaneimide (12 g, 6 8 mmol) and catalytic amount 2, 2' -Azo oxime (isobutyronitrile) treatment. The mixture was refluxed for 2 hours, cooled, transferred and evaporated. The oily residue was dissolved in DMF (10 mL) and added to sodium nitrite (0.32 g, 7.3 m. Example 1) Deprotonated 2_methyl-flavored (0.60 g '7.3 mmol) in DMF (10 ml). After stirring at room temperature for 12 hours, all volatiles were removed in vacuo and the residue was dissolved. Ethyl acetate. The organic phase was washed with water (3 times), dehydrated (sodium sulfate) and concentrated. Purified by chromatography [矽 ' 以 梯度 梯度 梯度 梯度 梯度 至 至 至 至 至 至 至 至 二 二 二 二 二/Aqueous ammonium hydroxide = 90:10:1) elution] The title compound was obtained as a light brown oil (0.98 g of '52%) as a light brown oil. Crystalline substance. Melting point 2〇 4 2 〇 5 ° C (melanol / diethyl ether), MS: m / e = 306 (M +). Example 113 1-(3.4-di- s- yl)-4-imidazol-1-yl-methyl-111 - Pyrazole sodium hydride (〇_24 g 55% in mineral oil dispersion, 5.5 mmol) was slowly added to a solution of the oxazole (0.19 g, 2-8 mmol) in DMF (15 mL). After 30 minutes of drop, the mixture was cooled in an ice bath and added with 4-methyl-methyl hydrazine-dialdehyde-stupyl one-time Η-ρ ratio (0.50 g, 1.9 mmol) resulting in a mixture of -68-

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Line This paper scale applies to Chinese national standards (CNS> Α4 specifications (210 X 297 mm) 1328584 A7 B7

The mixture was stirred at 20 ° C for 1 hour. After evaporating to remove the solvent, the residue was dissolved in ethyl acetate, washed with water, dried (sodium sulfate) and chromatographed [yield, with a gradient of methane to 30% (di-methane/methanol/aqueous ammonium hydroxide = 9 〇) :1〇:1) elution] 0.23 g (41%) of title compound was obtained. M.p. Example 114 was prepared according to the general procedure described in Example 113. Example 114 1-(3,4-Dioxaphenyl)-4-(2-methyl-°m-ol-1 -yl-methyl)-iH-nth 2-mercaptoimidazole was deprotonated using sodium hydride And then treated with 4-carbolyl _i-(3,4-dioxa-phenyl)-1 Η-ρ-butyrazole. Subsequent extraction and subsequent chromatography gave the title compound as a white crystalline solid. Melting point 176-177 ° C (ethyl acetate), MS: m / e = 307 (M+H+). Example 115 1 -imidazole, 1-(3.4-dichlorophenyl)-4-indole 1-(1 small imidazole-1- 8 plant, 1-, and 1H-imidazole, 1-(3,4-di V-V-氪-4-Π-ΠΗ-咮崠-i-V-ethyl 1- 1-[1-(3,4-di-phenyl)-1Η-imidazol-4-yl]- A mixture of ethanol (0.2 g, 0.78 mmol) and sulfinium chloride (3 mL, excess) was stirred at room temperature for 1.5 hours. The solvent was removed by a warm air stream. Then imidazole (3.5 gram 'excess) was added to the residue. The mixture was stirred at 90 ° C for 30 minutes. After adding water (1 mL), the mixture was extracted with di-methane. The organic phase was dehydrated (sodium sulphate). The solvent was evaporated. The residue was purified by chromatography.甲甲炫·/曱醇/aqueous hydroxide ==140:10:1 elution) to obtain 1H-bee bite, 1-(3,4-diphenyl)-4-[1-(1Η· azole) -Buji)-Ethyl]-(82 mg, 34%) was a light brown solid [MS: -69- This paper scale applies to Chinese National Standard (CNS) A4 size (210 X 297 mm) 1328584 A7 B7 V , invention instructions (66) m / e = 306.1 (M +)] and by-product 1H-imidazole, 1-(3,4-dichlorophenyl)-3-chloro-4·[1-(1Η-imidazole-1 -yl)-ethyl]-(10 2 mg, 38%) was a pale yellow oil. MS: m / e = 341.1 ( Μ + Η + ). Example 116 was prepared according to the procedure outlined in Example 115. Example 116 _1H-imidazole, 1-Π-Π-( 3,4-diqi stupid)-1Η-carbazole-4-one 1 ethyl 1-2-methyl b[1·(〗, 4-di-phenyl-phenyl)-1Η-味0^-4- The reaction of the ethanol with the subtropical helium, followed by the treatment with 2-methylimidazole, the subsequent work up of the extracts and chromatography gave the title compound as a light brown solid. MS: m/e=320.1 (M+). Example 117 1^-imidazole '1彳3.4-diqi stupyl)-4-丨1-(1-oxazol-1-one)-1-methylethyl 1- 2-[1-(3, a mixture of 4-dioxo-phenyl)-1Η-imidazol-4-yl]-propan-2-ol (150 mg, 0.55 mmol) and boron tribromide (1M in di-methane, 3 mL) Mix for 2 hours at room temperature. After removing the solvent under a stream of air, the residue was dehydrated overnight. Imidazole (226 mg, 33.2 mmol) was added and the mixture was stirred for 4 minutes on EtOAc. After water was added, the mixture was extracted with dioxane. The organic phase was evaporated (sodium sulfate) and evaporated. The title compound (15 mg, 8%) was obtained as a pale-yellow solid, m.p. Example 118 迅-味咬,?-甲华-1-Κ4-Γ3-(trifluoromethyl)裟裟ΜΗ-oxazol-2-one 1 'hydrochloric acid pound (1:2) -70- 1328584

1H-imidazole, 2·[(2-mercapto-1H-imidazol-1-yl)methyl]_4-[3-(trifluoromethyl)phenyl]-bu[[2·(tridecylfluorenyl) Ethoxy]hydrazino]-(0.034 g, 〇〇78 mmol) was dissolved in ethanol (0.8 mL) and treated with 2N hydrochloric acid (0.86 mL). The reaction mixture was refluxed overnight and cooled to room temperature and concentrated. The crude residue was taken in ethyl acetate and stirred at room temperature for 30 min. Filtration of 1H-imidazole, 2-mercapto-1-[[4-[3-(trifluoromethyl)phenyl]-1H.imidazol-2-yl]indolyl-, hydrochloride (24 mg' 81) %) is a pale yellow solid, MS: m/e = 307.2 (M+H+). Examples 119 through 122 were prepared according to the general procedure described in Example 118. Example 119 j_H-imidazole, hydrazine-["4-(4-fluoro-3-indolyl)-anthracene-&quot; oxazol-2-yl 1 methyl-2-methyl-, hydrochloric acid pound Π: 2 The title compound 'MS: m/e=270.1 (Μ+) is from 1Η-° rice, 4-(4-carb-3-phenylphenyl)-2-[(2-methyl-1H-imidazole) Preparation of -1-yl)fluorenyl]_i-[[2-(trimethyldecyl)ethoxy]indolyl]. Example 120 1K-Imidazole ' lf "4-(3,4-Difluorophenyl)-1 oxime-imidazol-2-yl 1 A-methyl-2-yl., salt sputum (1 -? Λ title compound, MS : m/e=275.2 (Μ+Η+) is from 1Η-°米唾, 4-(3,4-difluorophenyl)-2-[(2-indolyl-1Η-σ米嗤-1- Preparation of 1-[[2-(trimethylglycine)ethoxy]methyl]. Example 121 111-Miso '2-mercapto-l[~4-(4-methylthio) )基基~|·ΐΗ-η米岐-2-一1methyl-2-methyl-, hydrochloride (1:2) title compound, MS: m/e=285.2 (Μ+Η+) By 1Η-°m also, 2-[(2-71-

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Ordering This paper scale applies to Chinese National Standard (Cns) Α4 Specifications (210Χ 297 公爱) 1328584

Preparation of methyl-1H-imidazolyl)methyl]-4_[4-(indolylthio)phenyl]-l-[[2-(trimethylsulfonyl)ethoxy]methyl]. Example 122 - miso' fluoro-3-methyl jasmine V2.HH-carbazole-1-some-methyl,-,hydrochloride (1:2)

Heading compound, MS: m/e = 257.1 (M+H+) from 1H-imidazole, 4-(4-fluoro-3-indolylphenyl)_2-(1Η-imidazol-1-yl·methyltri Preparation of fluorenylalkyl)ethoxy]methyl]. Example 123. Dioxy-phenylindenyl-imidazolium-i-yl-methyl&gt;pyridine, hydrochloride π:η

To a suspension of sodium hydride (17 mg of 55% in mineral oil dispersion, 〇 39 mmol) in DMF (5 mL) was added 2-mercapto D-methane (3 2 mg, 0.39 mmol). The mixture was stirred at 20 ° C for 1.5 hours. Then 3·gasmethyl·5-(3,4-dioxa-phenyl)-acridinium hydrochloride (1:1) was added (100 mg' 〇·32 mmol Ear) and triethylamine (78 mg, 0.78 mmol), and the mixture was heated to i 〇〇 °c for 4 hours. After cooling, the title compound was obtained as a yellow oil. This material was dissolved in decyl alcohol, cooled to 4 ° C with stirring, and stirred and treated with hydrochloric acid/ethanol (1.46 Torr, 1.1 eq.) for 15 minutes. The solvent was removed in vacuo <RTI ID=0.0></RTI> to <RTI ID=0.0> MS: m/e = 317.1 (M+). Examples 124 through 127 were prepared according to the general procedure described in Example 123. Example 124 -72- This paper scale applies to China National Standard (CNS) A4 specification (210X 297 mm)

Title 3 Compound 'MS: m/e = 317. 〇(M+) is obtained as a light brown solid (60 〇 / 〇 yield) obtained by 2-pyringyl-3-(3,4- Dioxo-phenyl)-pyridine's hydrochloride (1:1) and 2-methyl miso were treated with sodium hydride and triethylamine as the 'reaction' followed by the formation of the hydrochloride. Example 125

(1:2) The title compound, MS: m/e = 317.0 (M+) was obtained as a color solid (yield: 51% yield). -Phenyl)·pyridine's hydrochloride (1:1) is reacted with 2-methylimidazole using sodium hydride and triethylamine as a base, followed by the formation of the hydrochloride salt. Example 126 phenyl)-5-imidazol-1-y-methyl·pyridine, hydrochloride π: Π title compound ' MS: m/e=304.1 (Μ+Η+) as solid (56% yield Obtained 'by obtaining 3-sulfonyl-5-(3,4-di-phenyl)-pyridine, hydrochloride (1:1) and imidazole using sodium hydride and triethylamine as the base The reaction is followed by the formation of the hydrochloride salt. Example 127 j_-(3,4-disorgano-styl)-5-(2-methyl-oxime-l-yl-indenylpyramine, hydrochloride π:η title compound, MS: m/e =332.2 (Μ+Η+) is obtained as an orange solid (49% yield) obtained from 3-methylmethyl-5-(3,4-di-phenyl)-py-73- Paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1328584

The bite 'hydrochloride (1:1) was used with 2-mercaptoimidazole. Sodium hydride and triethylamine were reacted as a base, followed by the formation of the hydrochloride salt. Example 128 1τ(.3,4 -mono-phenyl)-2-methyl-3-(2-methyl- sulty-1-yl-methyl-bito, hydrochloride Π: Π title compound, MS: m/e = 292.2 (Μ + Η +) was obtained as a ochre solid (77% yield) obtained from 3-carbazin-5-(3,4-di-phenyl)- 2 - mercapto-pyridine' hydrochloride (1:1) and 2-mercaptoimidazole (5 equivalents) using sodium hydride (3 equivalents) as a base, followed by the formation of the hydrochloride salt. Example 129 3_-(4- gas -phenyl)-5-(2-indolyl-imidazol-1-yl-methylpyridinium ο: 1) 3-bromo-5-(2-methyl-sodium-1-ylindenyl) -P ratio bite (120 mg, 0.48 mmol), hydrazine (triphenylphosphine) gasified palladium (Π) (1 〇 mg, 〇·〇 1 mmol) and potassium acetate (1403⁄4 g, 0.14 mmol) The mixture of the ears) was simmered in 2 liters (1 liters) at 2 Torr. The mixture was stirred for 1 hour, then 4-cyclophenyldihydroxyboric acid (78 mg, 〇.〇5 mmol) and 2N carbonic acid were added. Sodium solution (1.2 ml), the mixture was stirred at 1 Torr. (: argon atmosphere was heated for 7-24 hours. After cooling, solvent was evaporated and 2N sodium hydroxide (5 mL) and ethyl acetate were added. The mixture was shaken, the aqueous phase was separated, and then extracted with ethyl acetate. The organic extracts were washed with brine and dried over sodium sulfate, filtered and evaporated. The residue was chromatographed 2M ammonia in decyl alcohol = 97:3) elution]. The product was dissolved in decyl alcohol, cooled to 4 t with stirring, treated with hydrochloric acid/ethanol (1.46 Μ, 1.1 eq.) for 45 minutes, and evaporated at 50 ° C in high skin vacuum. The solvent was removed and dehydrated for 2 hours to give the title compound (98 mg, 64%) as a pale brown solid. MS: m/e=284.2 (M+H+). -74- The paper size was measured using Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) 1328584 A7 B7 Examples 130 through 142 were prepared according to the general procedure described in Example 129. Example 130 Monomethyl-bens)-5-(2-methyl-p-m-indol-1-yl-- Base)-|7 out of the salt hydrochloride π:η title compound, MS: m/e=277 (Μ+) via 3-bromo-5-(2-indolyl-imidazol-1-ylmethyl)- Pyridine was obtained by reaction with 3,4-dimethylphenyldihydroxyboronic acid as a pale yellow foam (54% yield). Example 131: 丄4-y-3 dimethylphenyl)-5- ( 2-Methyl rice bran-1 · a certain methyl buppyridinium salt (1:1 , title compound, MS: m/e = 281.1 (M+) via 3-bromo-5-(2-indolyl-imidazol-1-ylindenyl)-pyridine and 4-fluoro-3-methyl-phenyl Obtained by the reaction of diboric acid, it was a light brown foam (63% yield). Example 132 1 1 (3,4-Difluoro-phenyl)-5-(2-methyl-imidazol-1-yl-methylpyridine hydrochloride (1:1) title compound < MS: m/e=286.2 (M+H+) is obtained by reacting 3-bromo-5-(2-mercapto-ylidene-1-ylmethyl)-pyridine with 3,4-difluoro-phenyldihydroxyboronic acid, which is light yellow Bubbles (85% yield). Example 133 1^4-1-phenyl)-5-(2-indolyl-Nasaki·ι_基·甲一酸酸磅 π:1) Title compound, MS: m/e=268.3 (Μ+Η+) is obtained by reacting 3-bromo-5-(2-methyl--salt-1-ylmethyl)-pyridine with 4·fluorophenyldihydroxyboronic acid. Yellow foam (90% yield). -75- This paper scales through the currency @家标竿(CNS) domain (2lGX297 public)

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1328584

Example 134. Methyl-A-Curtain»(3_Trifluoromethyl hydrazine, ·pyridine π:η title compound, MS: m/e=318.3 (Μ+Η+) via 3-bromo- 5-(2-Methyl-sodium-1-ylmethyl)-, which was reacted with 3-trifluoromethylphenyldihydroxyboronic acid to give a 'yellow foam (74% yield). 135 Methyl-salt-1-yl-methyl)_% (4-trifluoromethyl-phenyl)-pyridine hydrochloride title compound, MS: m/e = 318.3 (Μ+Η+) 3-Bromo-5-(2-methylimidazol-1-ylmethyl)-pyridine was reacted with 4-trifluoromethylphenyldihydroxyboronic acid to give a 'yellow foam (77% yield). Example 136 gas-4-methyl-phenyl)·5-(2-methyl-imidazol-1-y-methyl)-pyridinium π:η title compound, MS·· m/e=298.3 (Μ+Η+) via 3-bromo-5-(2-methyl-imidazol-1-ylindenyl)-pyridine and 2-(3- gas·4-mercapto-phenyl)·4,4 ,5,5-tetradecyl[1,3,2]-dioxaindole borane reaction to give 'black solid (78% yield) 〇 Example 137 1_-(4·chloro-3-methyl -Phenyl)-5-(2.methyl-imidazole-1·a-methyl-)-sleeping salt (1:1, title compound, MS: m/e=298.3 (Μ+Η+) via 3- _5_(2_Methyl-imidazol-1-ylindenyl)-pyridine and 2-(4-carb-3-indolyl-phenyl)_4,4,5,5-tetramethyl

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1328584

[1,3,2]_Dioxaborane borane was obtained as a white solid (yield: 73%). Example 138: </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Bromo-5-(2-indolyl-imidazolyl-1-ylindenyl)-pyridine and 5-(4,4,5,5-tetramethyl[1,3,2]-dioxaborane borane -2-yl)·2,3-dihydrobenzoyl furan reaction, obtained as a pale yellow foam (18% yield). Example 139 - tetra-milk-5-yl-(2·甲某- P.m.-1 -yl-methyl) than the salt of the title compound, MS: m/e = 289.1 (M+) via 3-bromo-5-(2-indolyl-m. The fluorenyl group was obtained as a white solid (91 〇 / 与) with 2 - tetrahydroindenyl _5_yl _4 4 5 5 tetradecyl [1,3,2]-dioxaboron. Yield). Example 140 3(3__4 - gas-benyl)-5-(2-mercapto-salt-1-yl-methyl-p-picolinate π:η title compound, MS: m/e = 301.1 (Μ+) is obtained by the reaction of 3-bromo-5-(2-indolyl-methane-l-ylmethyl)-pyridine with 3-chloro-4-fluoro-phenyldihydroxyboronic acid as a yellow solid. (53% yield). Real $ 141 3-(4-Gas-3-trifluoromethyl-phenylmethyltolo-l-yl-methyl) dip, hydrochloride (1:1) Also, MS: m/ e=352.3 (M+H+) via 3-act-5-(2-methyl-imidazol-1-ylmethyl)-pyridine and 2-(4- gas-3-trifluoromethyl-phenyl) -4,4,5,5-four-77- This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm)

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Line 1328584 A7 - B7 V. INSTRUCTIONS (74) Methyl [1,3,2]-dioxaborane borane was obtained as a ochre solid (49% yield). Example 142 1-(4-Fluoro-3-tris.methyl-carotyl)-5-(2-methyl-imidazol-1-yl-methyl,pound hydrochloride (1:1) title compound, MS: m/e=336.3 (Μ+Η+) via 3-bromo-5-(2-methyl-imidon-1-ylmethyl)-ι» bite with 2-(4-fluoro-3-III The reaction was carried out by the reaction of fluoromethyl-phenyl)-4,4,5,5-tetramethyl[1,3,2]-dioxaindole borane as a white solid (6 〇0 / 〇 yield). Example 143 _1_H-imidazole, 2-ethyl-1-pyrene-"3-(trifluoromethylsulfanyl) gamma gamma 1 methyl 1-, decanoic acid test 1:2) Follow the general procedure described in Example 10, title The compound is obtained as a white crystalline material, which is obtained by first reacting [1-(3-trifluoromethylsulfanyl-phenyl)-p-imidazol-4-yl]-methanol with sulfoximine gas. It is then reacted with 2_ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Happiness 234-236 ° C (sterol / acetamidine) ' MS: m / e = 353 (M + H + Example 144 1H-imidazole, 2-mercapto-1-yron "1·"3 (trifluoromethylsulfanyl)methyl 1 methyl 1-, hydrochloride (1:2) as described in Example 10. A summary procedure in which the title compound is obtained as a white crystalline material. By first reacting [1-(3-trifluorodecylcarbophenyl)-1Η-miso-4-yl]-nonanol with argon, then with 2-methylimidazole and sodium hydride Reaction, followed by chromatography and crystallization of hydrochloride. Hyun-78- This paper scale applies to China National Standard (CNS) A4 specification (21〇X 297 public) 1328584

&gt; 200 ° C decomposition (methanol / ethylene), MS: m / e = 3 〇 3 (M + H +). Example 148 1ι[3-(1τ1-difluoroacetamidine)-phenylpyr-4.imidazole-i-ylmethyl-1Η·η-rhamazole hydrochloride (1:2)

The title compound was obtained as an off-white crystalline material according to the procedure outlined in Example 10, which was obtained by first using {1-[3-(1,1-difluoro-ethyl)-phenyl]-1Η-imidazole- 4-Gipoxime is reacted with sulfinium gas and then reacted with miso and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point &gt; 2 〇〇 &lt; t decomposition (sterol / diethyl ether), MS: m / e = 303 (M + H +). Example 149 JJj-° m. Sit ’ 1-ΓΠ-Γ3-Π.1-difluoroethyloxazole-4-芊] _mercapto 1-2-methyl-, hydrochloride Π: 2)

k Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material obtained by first using {1-[3-(ι,ι-difluoro-ethyl)-4-fluoro-phenyl] -1Η-imidazol-4-yl}-nonanol is reacted with sulfinium gas and then reacted with 2-methylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. 'Solution point &gt; 200 ° C decomposition (sterol / B puzzle), MS: m / e = 321 (Μ + Η +). Example 150 1-[3-(1,1-Difluoro-ethyl)-4-fluoro-benzene 1-4-°m 吐-1-A certain 1-1 only 〇 〇 地 盐 盐 Π: 2) Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material, which was obtained by first using {1-[3-(1,difluoro-ethyl)-4-fluoro-phenyl] -1Η-imidazole-4-ylbupropanol is reacted with sulfinium gas, then with imidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride salt. Melting point -80- The standard of Zhang is applicable to China National Standard (CNS) A4 specification (210X297 public) 1328584 A7 __B7 V. Invention description (77) &gt;200°C decomposition (methanol/diethyl ether), MS: m/e= 307 (M+H+). Example 151.1H - taste spit" 1-丨丨1-丨3-(~1,1·digasethyl)-4 - gas stupidity -1{^-°m saliva -4 -yl 1 methyl 1-2-ethyl-, hydrochloride Π: 2) Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material obtained by first using -(1,1-Difluoro-ethyl)·4-fluoro-phenyl]-1H-imidazol-4-yl}-methanol is reacted with sulfinium gas, and then reacted with 2_ethyl bite and sodium hydride, This is followed by chromatography of the chromatogram and the hydrochloride. Melting point &gt; 200 ° C decomposition (sterol / diethyl ether), MS: m / e = 335 (M + H +). Example 152 _1 Η ° ° 异 异 异 笨 笨 基 基 吐 基 基 基 基 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 1-2 Sexual Substance Acquired 'The method of obtaining it by first using [1-[3-(isopropyl-phenyl)- 1H-methylene-4-yl]-sterol to react with the sub-gas” and then with 2·曱The base sigma scent and sodium hydride reaction, followed by chromatography and crystallization of the hydrochloride. Melting point &gt; 2 〇〇 &lt;&gt; c decomposition (sterol / diethyl ether), MS: m / e = 281 (M + H +). Example 153 * jjj-imidazole '2-ethyl-1_丨丨1-Π-isopropyl 莫 • imidazole · 4 ] 芊 芊, hydrochloride (1:2) according to the general procedure described in Example 10, The title compound is obtained as an off-white crystalline material, which is obtained by first reacting [1-[3-(isopropyl-phenyl)- 1 Η-imidazol-4-yl]-methanol with sulfinium gas, and then 2_ethylimidazole and sodium hydride reaction' followed by chromatography and crystallization of the hydrochloride. Hyun Point &gt;2〇〇β(:

1328584 DESCRIPTION OF THE INVENTION Decomposition (sterol/accuracy), MS: m/e = 295 (M+H+). Example 15 4 4-Tat-1-ylmethyl-1-(3-(isopropyl-cage)_ih-p m.p. g. salt (1:2) according to the procedure outlined in Example 10 The compound is obtained as an off-white crystalline material obtained by first reacting with sulfinium gas using isopropyl-phenyl)·1H·imidazol-4-yl]-nonanol and then reacting with imidazole and sodium hydride, followed by For the chromatography and the crystallization of the hydrochloride. Hyun point 2〇〇_2〇6°C (sterol/B puzzle), MS: m/e=267 (M+H+). Example 155 jH-° rice vomit, 2-mercapto-purine-fri-(Mo-2-) sal-4-a-1 methyl 1-, hydrochloride (1:2) according to the procedure outlined in Example 10 'The title compound is obtained as a white crystalline material' obtained by first reacting (1 _茬_2_yl-1H-imidazol-4-yl)-methanol with sulfinium gas and then with 2-methylimidazole And sodium hydride reaction, followed by chromatography and crystallization of the hydrochloride. Mp 247-248 ° C (decyl alcohol / diethyl ether), MS: m / e = 288 (M+H+). Example 156 _1 _ _ imidazole ' 丄 3 - bromo-4-fluoro gamma V1H- 哞岫 -4- 1 methyl 1-2 ethyl, hydrochloride (1: 2) according to Example 10 The rough procedure 'the title compound is a white crystalline material obtained by first using [1-(3-Iso-4-fluoro-phenyl)-1H-miso-4-yl]-nonanol and sulfoximine gas. The reaction 'reaction then reacts with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 238-239eC (methanol / hexane), MS: m/e = 349 (M+H+). • 82. This paper scale applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1328584

Example 157. IH: imidazole, l-JLLi^g-bromo-4·gumyl viH-oxazole-4-芊]methyl]_2_methyl-, hydrochloride n:7丨 according to η example 10 The schematic procedure is as follows. The title compound is obtained as a white crystalline material obtained by first using [1_(3_bromo-4-fluoro-indolyl)_1Η_imivor-4-yl]-sterol and sulfinamide. The reaction is then reacted with 2-methylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 232_233 ° C (nonanol / diethyl ether), MS: m / e = 335 (M + H +). Example 158 iz (3-bromo-4-fluoro-bung imidazole-i-methyl- 1 Η-咄吔 酩 酩 In accordance with the general procedure described in Example 10, the title compound was obtained as a white crystalline material. By first reacting [1-(3-bromo-4-fluoro-styl)-1Η-sodium-4-yl]-methanol with sulfinium gas and then reacting with imidazole and sodium hydride, followed by chromatography Crystallization of hydrochloride and hydrochloride. Hyun spot 229-23 (TC (nonanol / diethyl ether), MS: m / e = 321 (Μ + Η +). Example 159

Jjj.-Imidazole, 1-ΓΓΜ3-Bie, a certain VlH-°-oxazole-4-a-1, a 1_2, a acetonide, hydrochloride (1:2V according to the schematic procedure described in Example 10, the title compound is grayish white The crystalline material is obtained by first reacting with sulfinium gas using [1-(3-ethyl-phenyl)·1Η·imidazol-4-yl]-methanol, and then with 2·methylimidazole and Sodium hydride reaction 'subsequent to chromatography and crystallization of the hydrochloride salt. Melting point &gt; 2 〇 (TC decomposition (methanol / diethyl ether), MS: m / e = 267 (M + H +). Example 160 - 83 - paper Zhang scale applies Chinese national standard (CMS) A4 specification (210 X 297 mm) 1328584 A7 _____B7 V. Invention description (8Q~Γ ~ 1H-imidazole, 2-ethyl-1-丨Π-Γ3·已篡芄V1H-carbazole, 4-indole, chlorate (1:2) The title compound was obtained as an off-white crystalline material according to the procedure outlined in Example 10, which was obtained by first using [1-(3). -Ethyl-phenyl)·1Η·Imidazol-4-yl]-nonanol is reacted with sulfinium gas, then reacted with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point &gt; 2〇〇〇c decomposition (sterol / Ether), MS: m/e = 281 (M+H+). Example 161 1-(3-ethyl-phenyl)-4-[upsilon]-l-ylmethyl-iH- miso salt brewing _ The schematic procedure described in Example 10, the title compound, was obtained as an off-white crystalline material obtained by first using [1_(3-ethyl-phenyl)·1Η_°m-4-yl]-methanol and awakening. The gas reaction 'then reacts with the saliva and the argon nanon' followed by the chromatography and the crystallization of the hydrochloride. Melting point &gt; 丨9〇ec decomposition (sterol/ether), MS: m/e=253 (M+ H+). Example 162 JH-imidazole '1-ΓΓ1-Ρ-cyclopropanyl-methyl}_1H-mashed _4_其]甲早卜0 methyl-, pound acid pound (〗 〖?) Follow the example 10 The summary procedure, the title compound is obtained as a light brown crystalline material, which is obtained by first reacting [1_(3·cyclopropyl]1H-imidazol-4-yl]-methanol with sulfinium chloride, and then Reaction with 2_mercaptoimidazole and sodium hydride, followed by crystallization of the chromatographic and hydrochloride salt. mp 174 _ 175 ° C (methanol / diethyl ether), MS: m/e = 279 (M+H+). -ΓΓ1-Γ3-difluoromethyl·4_fluorophenyl)·1Η_哔味_4·一一甲美本纸Scale Fits s s home standard (CNS) Α 4 specifications (21GX 297 public) -84- 1328584 A7

1-2-Methyl-, salt hydrazine: 2| The title compound was obtained as a white crystalline material according to the procedure outlined in Example 10, which was obtained by first using dimethyl fluoromethanone- Ιηκ4_基]-sterol reacts with a suffocating gas, and then reacts with 2.····················· Melting point: 223-225 C Decomposition (methanol/ethyl bond), ms: m/e = 306 (Μ+). Example 164 '1. 丨丨 丨丨 笨 咄 1-2 1-2-ethyl-, hydrochloric acid was transferred according to the general procedure described in Example 10, the title compound was obtained as a white crystalline material obtained by first using Η-ρ. Difluoromethyl _4 fluorophenyl]-1 Η imidazolyl-4-yl]-methanol is reacted with sulfinium chloride and then reacted with 2 ethyl hydrazine and mouse sodium. 'Next to chromatography and hydrochloride Crystallization. Melting point 229-232 ° C decomposition (sterol / ether), MS: m / e = 320 (Μ + ). Example 165 Bis(3-difluoroindolyl-4-fail-loading)-4-°Chosing &lt;-1-ylmethyl1-1 Η-ρm salic acid hydrazine n: 2) According to Example 10 Briefly described, the title compound is obtained as a white crystalline material obtained by first using [1-(3-difluoroindolyl-4-fluoro-phenyl)-1Η-imidazol-4-yl]-methanol with The sulfinium chloride is reacted and then reacted with imidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 23 9-24 1 eC Decomposition (sterol/accuracy) ' MS: m/e = 292 (M+). Example 166 j_H-imidazole, 2-ethyl-lmnf formazan, acetonide-imidazole-4-yl 1 A-85- This paper scale applies to China National Standard (CNS) A4 specification (2i〇x 297 public )

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1328584 A7 B7 V. INSTRUCTIONS (82) :- Base, Hydrochloric acid Pound (Ί·7| According to the rough procedure described in Example 10, the title compound is obtained as an off-white crystalline material] obtained by first using π_(3_? Sulfur-phenyl-phenyl)-m-sodium-4-yl]-methanol is reacted with chlorinated chlorobenzene and then reacted with 2-ethyl sulphonate and sodium hydride, followed by chromatography and crystallization of the hydrochloride Melting point &gt; 200 C decomposition (sterol / diethyl ether), ms: m / e = 299 (M + H +). Example 167 ox-carbazole, 2-methyl-1-ΙΙ1ι£1^ (methyl sulphur) Stupid base 1-1H-呻 is ―/) 健]methyl 1-, hydrochloride Π: 2, according to the general procedure described in Example 10, the title compound is obtained as an off-white crystalline material, obtained by first use [ Xenon thiol-alkyl-phenyl)-1 Η-imidazol-4-yl]·methanol is reacted with sulfinium gas, then reacted with 2-methylimidazole and sodium hydride, followed by chromatography and hydrochloric acid Crystallization of salt. Melting point &gt; 200eC decomposition (methanol / ether), MS: m / e = 285 (Μ + Η +) » Example 168.坐-1-ylmethyl·1_(3_methylsulfanyl-methyl)_1Η•咗a ( (: 2) Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material. It is obtained by first reacting [1-(3-methylsulfanyl-phenyl)-1Η-imidazol-4-yl]-nonanol with sulfinium gas and then reacting with imidazole and sodium hydride, followed by For the chromatography and the crystallization of the hydrochloride. Melting point &gt; 2 〇〇 t solution (sterol/diethyl ether), MS: m/e = 271 (M+H+). Example 169 1_H-imidazole '2-B--1-丨" 1-丨3-(trifluoromethane) Mo Mo·)-1Η•呼倍] -86- This paper scale adopts Chinese National Standard (CNS) Α4 specifications (210Χ297 mm) 1328584 A7 ___B7 V. Description of the invention (84) 1-, guanidine hydrochloride: 2> According to the general procedure described in Example 10, the title compound was obtained as a white crystalline material, which was obtained by first using ^气弘vinyl-phenyl) 1Η_ 嗤-4-yl]-nonanol reacts with sulfinium gas, and then reacts with 2_mercaptoimidazole and sodium hydride, followed by chromatography and crystallization of hydrochloride Melting point 207-208 decomposition (methanol / sigma), MS: m / e = 265 (M + H +). Example 173 1H-imidazole, 1-indole 1-(3-indolyl)-1Η-imidazole-4 - Its 1A early flight, 曱, HCl salt: 2) Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material. The method was obtained by first using [丨气^气·phenyl) _1 oxazol-4-yl]•methanol is reacted with sulfinium chloride and then reacted with 2_mercaptoimidazole and sodium hydride. Then followed by chromatography of chromatographic and hydrochloride. Melting point &gt; 2〇〇t: decomposition (sterol / Ether), MS: m/e = 273 (M+H+). Example 174 m. s. 1 - 『1 - (3· 笨 基 基 基 基 基 1-2, 1-2, HCl salt: 2) Following the general procedure described in Example 10, the title compound was obtained as an off-white crystalline material obtained by first using [1_(3_qi_phenyl)_115_imol-4-yl]-sterol and sulfinic acid. Chlorine reaction, then reacted with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of hydrochloride. Melting point &gt; 2 〇〇 ^ decomposition (sterol / ether), MS: m / e = 287 (M+H+). Example 175 1-(3- gas-stupyl)-4-°m-kilo-1-ylmethyl-1H-segmented pound-cool -88 - This paper scale applies to Chinese National Standard (CNS) A4 size (210 X 297 mm) 1328584 A7 _____B7 V. Description of invention (85~) ~ 'According to the rough procedure described in Example 1 ,, the title compound was obtained as an off-white crystalline material obtained by first using [1_( 3_Gas_Phenyl)_11€_Imidazol-4-yl]-nonanol is reacted with sulfinium chloride and then reacted with imidazole and sodium hydride' followed by chromatography and crystallization of the hydrochloride salt. Decomposition 2001 (sterol/diethyl ether), MS: m/e = 259 (M+H+). Example 176 1H-flavored sitting, 1-171-(3- moth-salt spit-4-yl 1 methyl 1-2-methyl-, hydrochloride (1:2) Follow the general procedure described in Example 10. The title compound is obtained as an off-white crystalline material obtained by first reacting phenyl)_11{_imidazol-4-yl]-nonanol with a subtropic gas, and then with 2 曱 咪 咪 及 and sodium hydride The reaction is followed by chromatography and crystallization of the hydrochloride salt. Hyun spot &gt; 222 °c decomposition (sterol / ether), MS: m / e = 365 (M + H +). Example 177 1H-Mi. Sit '2·Ethyl-1-丨丨1-“3-fluoro-5-(trifluoromethyl)芏篡·|·1Η•imidazole·4-yl 1methyl 1-, hydrochloride (1: 2. Following the general procedure described in Example 10, the title compound was obtained as a white, crystalline material obtained by first using [^-(3-fluoro-5·trifluoromethyl-phenyl)-1Η-imidazole- 4-Methoxy]-methanol reacts with sulfinium gas and then reacts with 2-ethyloxypropene and weathered ammonia' followed by chromatography and crystallization of the hydrochloride. Melting point. 243-244 ° C (methanol / ether ), MS: m/e = 338 (Μ+). Example 178 1 Η-taste, 1-rn-f3-fluoro-5-(tris-arylmethyl)methyl 1-1H-. 1 methyl 1-2-methyl-, continuous acid π: 2) -89- This paper scale is applicable to Chinese national standards (CNS> Α4 specification (210Χ 297 mm) 1328584 A7 B7 Five invention descriptions as described in Example 10 For the general procedure, the title compound is obtained as an off-white crystalline material obtained by first making ffl [1_(3·曱____trifluoromethylphenyl)·1Η-imidazole-4·yl]• sterol Reacts with sulfinium chloride, then reacts with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride Melting point 245-246 ° C (sterol / ethylene), MS: m / e = 350 (Μ +).

Isoxazole-1-methyl-1 was obtained according to the general procedure described in Example 10, and the title compound was obtained as a white crystalline material, which was obtained by first using [1-(3-methoxy-5-trifluoromethyl) Stupid)-1Η-imidazol-4-yl]-nonanol and sulfinamide, then react with imidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride, melting point 244_246 °C decomposition (methanol) /ether), MS: m/e = 322 (Μ+). Example 183 jji-imidazole 'T-butyl phenyl group V1H-oxazolyl-4- even 1 Azyl? Methyl group; I-, hydrochloric acid pound (1:2) Following the general procedure described in Example 10, the title compound was The off-white crystalline material is obtained in a manner obtained by first reacting [1-(3-tert-butyl-phenyl 1H-imidazol-4-yl)-nonanol with sulfinium gas, and then with 2-methyl The taste of saliva and sodium sulphate' followed by the crystallization of the chromatographic and hydrochloride. Hyun point &gt; 2 〇〇. 〇 decomposition (methanol / sigma), MS: m / e = 295 (Μ + Η +) Example 184 1_Η-imidazole, 1-"Π-(3-t-butyl-methyl-V1H-咮岵-zu-1, a certain μ2_methyl1-2-ethyl-, hydrochloride π:2) -91 - This paper size is applicable to the Chinese National Standard (CNS) Α4 specification (210 X 297 mm) 1328584 A7 B7 V. Inventive Note (88) According to the general procedure described in Example 10, the title compound is obtained as a light brown crystalline material. 'The method of obtaining is by first reacting the third butyl-phenyl)-1H-imin-4-yl]-sterol with sulfinium gas and then reacting with 2-ethylimidazole and sodium hydride. Chromatography and crystallization of hydrochloride. Hyun point 2〇5.匚 decomposition (methanol/b test), MS: m/e = 309 (M+H+). Example 185 1-(3-Terti-l-yl)-4-imidazole-1·A certain ·1Η•imidic acid π:2, according to the general procedure described in Example 10, the title compound was grayish white crystal Obtaining substances obtained by first reacting with sulfinium gas using [1-(3-t-butyl-phenyl)-1H-imidazol-4-yl]-methanol and then reacting with imidazole and sodium hydride 'The receiver is the crystal of chromatography and hydrochloride. Hyun point &gt; 200*^ decomposition (methanol/diethyl ether)' MS: m/e = 281 (M+H+). Example 186 j_H-side. 嗤, gas · 4 · (Sanzu 曱 )) phenyl ΐΗ ΐΗ diimidazole _ 4 its 1 methyl 1-2-methyl-, hydrochloride (1: 2, in accordance with the example 1 〇 The summary procedure 'the title compound is obtained as a white crystalline material' is obtained by first using [ip-gas trifluoroantimony·stupyl)-1 Η-D m-sial-4-yl]-sterol and sub The helium gas reacts and then reacts with methyl oxazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 221-222°C (methanol/j-mystery), MS: m/e=357 (M+H+) 实例 Example 187

1Η-imidazole, 1-indoleyl 2_ethyl·, according to the schematic procedure described in Example 1 ,, the title compound is white crystalline material -92· 1328584 A7 B7

Obtained, obtained by first reacting [1-(3- gas·4-trifluorooxo-phenyl)-1Η-imidazol-4-yl]-nonanol with sulfinium chloride] and then with 2 The reaction of carbazole and sodium hydride is followed by chromatography and crystallization of the hydrochloride. Melting point &gt; 250 ° C (nonanol / diethyl ether), MS: m / e = 370 (Μ +). Example 188 Gaso-4-trifluoromethane-phenyl)-4-imidazol-1-ylmethyl-1 oxime-flavored bite (1:2) Following the procedure outlined in Example 10, the title compound was white crystal. Obtaining substances obtained by first reacting [1-(3-chloro-4-trimethoxymethoxy-phenyl)-1Η-imidazol-4-yl]-nonanol with sulfinium gas, and then The reaction of imidazole and sodium hydride is followed by chromatography and crystallization of the hydrochloride. Hyun 2丨2-213 (methanol/acetamidine), MS: m/e=342 (M+). Example 189 Ιϋ-Mi嗤' 1-ΓΠ-Γ3-[difluoroanthracene) jasmine i_iH-imidazole-4-篡1 methyl 1-7-ethyl-, hydrochloric acid was transferred according to the general procedure described in Example 10, title The compound is obtained as a white crystalline material, which is obtained by first reacting [1-(3-difluoroindoleoxyphenyl)-1H-amido-4-yl]-nonanol with sulfinium gas, and then Reaction with 2_ethylimidazole and sodium hydride' followed by chromatography and crystallization of the hydrochloride. Mp 216-217 ° C (methanol / diethyl ether), MS: m/e = 319 (M+H+). Example 190 jjj·imidazole, dioxane gas) 袈i i_iH-imidazole-4-l 1 methyl 1-2-whenyl-, hydrochloride Π: 2) Following the general procedure described in Example 10, the title compound was white Crystalline substance-93- This paper size is suitable for towel gg home material (CNS) Α4 specification (21Q χ297 public) 1328584 A7-B7 V. Invention description (90) Obtained 'the method of obtaining it by first using [1-(3 -difluorofluorenyl-phenyl)_ 1H-imidazole-4-yl]·nonanol is reacted with sulfinium chloride and then reacted with 2_mercaptoimidazole and sodium hydride' followed by chromatography and hydrochloride crystallization. Mp 22 〇 222 ° C (methanol / diethyl ether), MS: m, e = 305 (Μ + Η +). Example 191 - Root 'helium-stupyl-mercapto-l-yl-methyl- ton-salt salt according to the general procedure described in Example 10, the title compound was obtained as a white crystalline material's method of obtaining it by first use [ 1_(3_Difluoromethoxy-phenyl)_ 1Η-imidazol-4-yl]-nonanol is reacted with sulfinium gas and then reacted with imidazole and sodium hydride' followed by chromatography and crystallization of hydrochloride . Hyun points 2〇5_2〇6. 〇 (sterol / diethyl ether), MS: m / e = 291 (Μ + Η +). Example 192 1_Η-° meters. Sit, l-rn-(U stupyl)-iH-imidazole-4-one 1 formazan μ2_甲某_, hydrochloride Π: 2) According to the general procedure described in Example 10, the title compound is a light brown crystalline material. Obtained, obtained by first reacting with sulfinium gas by [丨丨夂 bromo-phenyl)_1Η•imidazol-4-yl]-methanol, and then reacting with 2-methylimidazole and sodium hydride. Analysis and crystallization of hydrochloride. Hyun point 205-207 ° C (methanol / diethyl ether), MS: m / e = 317 (M + H +). Example 193 1H-Mi-t-dichloromethyl)phenyl μ1Η咄唆_4_yl 1 A ··2_ethyl-, hydrochloride (1:2) Following the procedure outlined in Example 1 ' Obtained as a white crystalline material obtained by first applying the Difluoromethyl-phenyl)-94-sheet size to the Chinese National Standard (CNS) A4 specification (210X297 mm).

k 1328584 A7 ____B7_ V. Description of the invention (91 ~) · ^ 1H·imidazol-4-yl]-nonanol reacted with sulfinium chloride, then reacted with imidazole and sodium hydride, followed by chromatography and hydrochloride crystallization. Melting point 2l9_22〇=c (methanol / diethyl ether)' MS: m/e = 303 (M+H+). Example 194, l-"fi-"3-(difluoromethyl) phenyl i-iH- oxazole _4_ 11 甲 曱 曱 ,, HCl HCl according to the general procedure described in Shell 10, the title compound Obtained as a white crystalline material's obtained by first reacting [1_(3-difluoroindolyl)phenyl-1H-imidazol-4-yl]-nonanol with sulfinium gas, and then with 2_ The mercapto imidazole and the sodium hydride reaction are followed by chromatography and crystallization of the hydrochloride. Melting point 195_196 °C (sterol/acetamidine), MS: m/e = 289 (M+H+) » Example 195 1-(3-difluoromethyl-phenyl)-4-imidazol-1-yl The carbazole hydrochloride salt (1:2, according to the general procedure described in Example 10, the title compound was obtained as a white crystalline material obtained by first using [丨-^-difluoroindolyl-stupyl)_ 1H -&quot;M.sup.4-yl]-nonanol reacts with Qiqi and then reacts with imidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride salt, mp 216-217. (: (sterol / riddle), MS: m/e = 275 (M+H+). Example 196 ί 1-Γ1-(3,4-two-gas-stupid V1H-咄吔-4- a·A 1-1H-imidazole-2-yl} fluorenyl-amine, H Π [ [1-(3,4-di-phenyl)-iH-imidazol-4-yl-indenyl-1H-imidazole -2-yl}-amine (〇·7 g, 2.3 mmol) was refluxed for 2 hours in a suspension of triethyl orthophthalate (1 ml). The reaction mixture was evaporated to dryness and dissolved in ethanol ( 10 ml) and __ -95- This paper size applies to the gg standard (CNS) such as specifications (21QX Ngong Gong Ai) 1328584 A7 ____B7 V. Invention description (92~) ' Cooling in ice bath. Add sodium borohydride (0 09 i g, 2 4 mmol), the mixture was allowed to slowly reach 20 C. After 18 hours, ethyl acetate and brine were added and the organic phase was separated, dried (sodium sulfate) and concentrated. The ruthenium gel was obtained by using a gradient of methane methane to ioo 〇 / 〇 (dichloromethane / methanol / aqueous ammonium hydroxide = 9 〇: 1 〇: 1) eluted to give the title compound as a free base. (0.25 g, 16 〇 / 〇). Melting point &gt; 25 (rc (methanol / diethyl ether), Ms: claws such as (M + H +). Example 197 [3-_( j., 4-diqi-phenyl)-5-(2-methylamine _imidazole-indole_early carbazole-4-yl-1-methanol 醢 Π Π ·" {1-[1-( 3,4-dioxa-phenyl)_1Η-imidazol-4-yl-indenyl]-1Η-imidazole-2-yl}·methyl-amine (0.60 g, 1.7 mmol) in acetic acid (7 mL) And aqueous furfural (2 ml 37% solution) was mixed at 20 C for 96 hours. The reaction mixture was evaporated to dryness and chromatographed [矽胶' with a gradient of dioxane to 5 % (dioxane / methanol). Aqueous Ammonium Hydroxide-90_10·1) Elution] The free title of the title compound was obtained. The crystals were obtained as pale white salt (0.030 g, 5%). Melting point &gt; 180»c decomposition (methanol / diethyl ether), MS: m/e = 352 (M+H + ). Example 198 1H-flavor __i__-act-5-fluorocarbyl ton-4-yl 1 methyl 1-2-methyl-, hydrochloride Π: 2 The title compound was obtained as an off-white crystalline material according to the procedure outlined in Example 10, obtained by [1-(3-bromo-5-fluoro-phenyl)-m-imidazole-4-yl]-sterol First reacted with sulfinium gas, then with 2_mercaptoimidazole and sodium hydride, followed by chromatography and crystallization of hydrochloride. Melting point &gt; 2〇〇π decomposition (-96- paper Degree of Chinese yuzhen of Standards (CMS) Α4 Specification (210X 297 mm) 1328584 A7 B7 invention described five (93 methanol / ethyl mystery), MS: m / e = 335 (M + H +). Example 199 1H-imidazole, 1-indole "1-(3-bromo-5-fluoromethane V1H-imidazole-4-yl-1methyl-hydrochloride hydrazine: 2) Follow the general method described in Example 10. Obtaining the title compound as an off-white crystalline material obtained by the method of first using [1·(3_漠·5_fluoro-phenyl)-1Η-°m嗤-4-yl]-methanol and Gas reaction, then reacted with 2_ethyl spray and sodium hydride, followed by chromatography and crystallization of hydrochloride. Melting point &gt; 200 ° C decomposition (methanol / sigma), MS: m / e = 349 (Μ+Η+). Example 200 Binding odor-5-gas-bens)-4-flavin-1-yl-methyl _ΐΗ-ρ米素磅酸験According to the general method described in Example 10, the title compound was obtained. Obtained as an off-white crystalline material obtained by first reacting with sulfinium gas using π_(3_bromo-5fluorophenyl)-1Η-imidazol-4-yl]-methanol, followed by reaction with imidazole and sodium hydride , followed by chromatography and crystallization of the hydrochloride. Melting point &gt; 2 〇〇. 匸 decomposition (sterol / ethyl acetonide), MS: m / e = 321 (Μ + Η +). Example 201 line abazole, 1-丨Γ1-(2.2-Difluoro-1.3-indole, acoustic 嗤-4-yl 1 methyl 1-2-ethyl-, salt Acid salt π: 2) Obtained the title compound as a white crystalline material according to the procedure of Example 10, obtained by first using ^·^^-difluorobenzopyrene, 3]dioxol-5 ··················································································乙越), MS: m/e=333 •97· 1328584 A7 _ 丨1 - B7 V. Description of the invention (94) (M+H+) 〇Example 202 Salivation 'diox·ι_3-mosa and two gases- 5-Base)-1Η·Mimray-4-yl 1A hydrazine 1·2-A--, lithium benthoic acid (1:2) According to the general method described in Example 10, the title compound was obtained as a white crystalline material. It is obtained by first reacting with sulfinium gas using ^-(2-difluoro-benzopyrene, 3]dioxoin-5-yl)-1Η-imidazol-4-yl]-nonanol. Then, it is reacted with 2-methylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride salt. Melting point &gt; 250. (: (sterol/diethyl ether), MS: m/e = 319 (M+H+) Example 203 1 bis (.?_,2·difluoro-benzo[1,31 dichloro-inden-5--V4-imidazole-1-yl-methyl) -1H-imidazolium hydrochloride was obtained according to the general procedure described in Example 10 to obtain the title compound as a white crystalline material. The obtained method was obtained by first using 1^-(2,2-difluoro-benzo[1,3]. Dioxan-5-yl)·1Η-imidazol-4-yl]-methanol reacts with the sub-gas, and then reacts with the taste and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Hyun point 245-246 ° C (sterol / acetamidine), MS: m / e = 3 19 (Μ + Η +). Example 204 ?-f4-(2-Methyl---------------------------------------------------------------------------------------------------------------------------------- The method of obtaining is by first reacting with [Qi Lin_2_yl-1H-Miso-4-yl)-methanol and then reacting with the submerged flue gas and then reacting with 2_methylhydrazine and sodium hydride] followed by chromatography And crystallization of the hydrochloride salt, m.p. -98- The paper size is applicable to China National Standard (CNS) A4 specification (210X297 public firefly) 1328584 A7 B7__ V. Invention description ^ ) — ~—:- Example 205 U4-〇乙棊一甲V imidazole·1· base 1. According to the general method described in Example 10, the title compound was obtained as an off-white crystalline material. The obtained method was obtained by first using (1_porphyrin-2_*_1η_miso-4-yl)-methanol and sub- The sulfonium chloride is reacted and then reacted with 2-ethylimidazole and sodium hydride, followed by chromatography of the chromatographic and hydrochloride. Melting point &gt;8〇β(:decomposition (ethyl acetate/hexane), MS: m/e=304 (M+H+) » Example 206 h (4-imidazole-1-yl-methyl-capsule·1; _ base) ^ apricot shouting according to the general method described in Example 10 'obtained the title compound obtained as an off-white crystalline material obtained by first using (1-porphyrin-2-yl-1H-propan-4-yl)- Methanol reacts with sulfinium chloride and then with imidazole and sodium hydride' followed by chromatography and crystallization of the hydrochloride. Hyun> &gt; 15 〇. (: Decomposition (ethyl acetate / hexane), MS: m /e=276 (M+H+). Example 207 1ϋ------丨-丨-4-(trifluoromethyl) 笨 基 1H-imidazol-4-yl 1-methyl 1-2-B -,, 骧 Π Π: 21 Obtained the title compound as a white crystalline material according to the general method described in Example 10, which was obtained by first using [1-(3- gas-4-trifluoromethylsulfanane). Benzyl-phenyl)-1Η-imidazol-4-yl]-methanol is reacted with sulfinium chloride and then reacted with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride salt. 215 ° C (methanol / diethyl ether), MS: m / e = 387 (M + H +). Example 208 1H-imidazole, 1-ΓΓ1- Ρ-Gas-4-(Trifluoromethyl) Benzene 篡μΐΗ-Imidazole·4·一1-.99 This paper scale applies to Chinese National Standard (CNS) Α4 Specification (210 X 297 mm) 1328584 A7 B7 Five , invention description (96~~) methyl 1-2-methyl-, lithinate (1:2) According to the general method described in Example 10, the title compound was obtained as a white crystalline material, which was obtained by first Reaction with [1-(3- gas-4-trifluoromethylsulfanyl-phenyl)-1Η-imidazol-4-yl]• sterol with sulfinium chloride, followed by 2-methylimidazole and hydrogenation Sodium reaction, followed by chromatography and crystallization of the hydrochloride salt mp 195-198 ° C (methanol / diethyl ether), MS: m / e = 373 (M+H+). -Trifluorodecylsulfanyl-styl V4-°oxazol-1-ylmethyl-1H-imidazole hydrochloride Π: 2) Obtained the title compound as a white crystalline material according to the procedure outlined in Example 10 , obtained by first reacting with [1 -(3- gas-4-trifluoromethylsulfanyl-phenyl)-1Η-[methane-4-yl]-methanol, and then reacting with the arsenic gas, and then Reaction with imidazole and sodium hydride' followed by chromatography and crystallization of the hydrochloride. Melting point 244-245 ° C (sterol/diethyl ether), MS: m/e = 359 (Μ+Η+) » Example 210 3- H-(2-ethyl-imidazole-1·A certain V imidazole-1-yl-1-+ The title compound was obtained as an off-white crystalline material according to the general method described in Example 10, which was obtained by first using (1_porphyrin-3-3·1H_imidazol-4-yl)-nonanol and yttrium. The reaction is then reacted with 2-ethyl oxazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 132_丨361 (ethyl acetate / hexane). MS: m/e = 304 (M+H+). Example 211 3-"4-(2-methyl-feed--1-ylmethyl-peak-1-based apricot said following the procedure outlined in Example 10) to obtain the title compound as an off-white crystal -100-

1328584

Obtaining substances obtained by first reacting (1_porphyrin_3·*_1Η·salt-4-yl)-sterol with sulfinium chloride and then reacting with 2·nonylimidazole and sodium hydride , followed by chromatography and crystallization of the hydrochloride. Melting point 168_172β (: (ethyl acetate / hexane), MS: m / e = 290 (Μ + Η +). Example 212 / 1: gas - 2 · "4-(2-mercapto-ton-1-yl) A. Ball ···················································································· 1Η-imidazol-4-yl]-nonanol is reacted with sulfinium gas and then reacted with 2_mercaptopurine and sodium hydride' followed by chromatography and crystallization of the hydrochloride. Melting point 192-196 °C (ethyl acetate / hexarene), MS: m / e = 274 (Μ + Η +). Example 213 1: chloro-2-indole 4-(2-ethyl-°m啥-1-yl-methyl The saliva group was obtained according to the schematic procedure described in Example 10 to obtain the title compound as an off-white crystalline material obtained by first using a gas pyridine·2-yl)-1 Η-imidazol-4-yl]-nonanol and sulfoximine gas. The reaction is then reacted with 2·ethyl oxime and sodium hydride. The chromatographic and hydrochloride crystals are then clarified. 182-185 ° C (ethyl acetate / hexane), MS: m/e = 288 (Μ+Η+). Example 214

Ui-(2·曱基-咪_嗓-1_ mercapto-oxazol-1-yl-isoindole-pound pp was obtained according to the schematic procedure described in Example 10, and the title compound was obtained as an off-white crystalline material. The method of obtaining is carried out by first reacting (丨_isoporphyrin-3-yl-1H-imidazol-4-yl)-methanol with sulfinium gas, and then reacting with 2-mercapto miso and sodium hydride, followed by layer Crystallization and crystallization of hydrochloride. Melting point &gt;25〇&lt;t( • 101 - The paper scale applies to China National Standard (CNS) A4 specification (210X 297 public) 1328584 A7

Sterol/diethyl ether), MS: m/e = 290 (M+H+). Example 215 1 ^-°Feng Tu '2-ethyl-1-丨丨1-丨4-(three gas gas) stupid base 1_; [only _ 〇 〇 &lt;|?-4-芊1_ 曱基1 -, pounds of hydrochloric acid (Ί: 2, according to the general procedure described in Example 10, 'obtained the title compound as a white crystalline material obtained' obtained by first using [1-(4-tris-oxy-phenyl)-1Η] - Met-4-yl]-sterol reacts with the subsequent gas, and then reacts with 2-ethyl sulphate and sodium hydride' followed by chromatography and hydrochloride crystallization. Hyun point 216-218 ° C (sterol/diethyl ether), MS: m/e = 337 (M+H+). Example 216 HU sniffer, 2-mercapto-1-in1-in 4-(trifluoromethane) jasmine-m-imidazole ice早^ 曱1, hydrochloride Π: 2) Obtained the title compound as a white crystalline material according to the procedure outlined in Example 10, obtained by first using [1-(4-trifluoroantimony-benzene) Base) -1 Η - ° m. The benzyl-4-yl]-nonanol reacts with the helium gas and is then reacted with 2-mercaptoimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride salt. Melting point 23 1-233 ° C (decyl alcohol / diethyl ether), MS: m / e = 323 (M+H+). Example 217 1H-imidazole, 1-"Γ1-Π-Lianza-3-V1H-imidazol-4-yl 1 A certain 1-2-methyl _, hydrochloride (1:2) 1H-imidazole, 1 -[[1-(3-Iodophenyl)-iH-imidazol-4-yl]-indenyl]-2.indolyl (0.20 g '0.55 mmol) in suspension of toluene (1 mL) The solution was treated with hydrazine (triphenylphosphine) palladium (0.023 g, 0.02 mmol) (under argon). After 30 minutes, add phenyl diboric acid (0.080 g, 0.66 mmol) and 2M carbonic acid unloading -102. This paper scale applies to China National Standard (CNS) A4 specification (210X297 public) 1328584

Water / gluten (2 · 0 ml). The reaction mixture was refluxed for 2 hr then extracted with ethyl acetate and water. The organic phase is dehydrated (sodium sulfate), concentrated and chromatographed [j. The free base of the title compound was obtained as a colorless oil ( 13 g, 75%). It is white hydrochloride crystals. Melting point 241_243»c (methanol / diethyl ether), MS: m/e = 315 (M+H+). Example 218 JJj-imidazole, 2-ethyl-1-indole 1 · "4 · (tri-argonylthio) benzoxazole 1 1 methyl 1-, hydrochloride (1:2) according to Example 10 By way of summary, the title compound is obtained as a pale yellow crystalline material obtained by first using [i_(4-trifluoromethylsulfanyl-phenyl)-1Η-imidazol-4-yl]-sterol with The sulfinium is reacted with helium and then reacted with 2_ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Happiness 183-185 ° C (sterol / B-over), MS: m / e = 352 (M +). Example 219 ia: ° rice bran, 2-mercapto-1-"--"4_(three n-methylthio) moxa rabbit _4_ a 1 thiol 1-, hydrochloride (1:2) according to the example 10, the general method, obtaining the title compound as a white crystalline material, obtained by first using [1_(4·trifluoromethylsulfonyl-phenyl)-1Η-imidazol-4-yl]-oxime The alcohol is reacted with sulfinium gas and then reacted with 2_mercaptoimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Melting point 249-250 C (sterol/B test), MS: m/e = 3 3 9 (M+H+). Example 220 6-"4-(2-Methyl-imidazol-1-ylformamidine)-imidazole_Buji [Fenglin-103- 'This paper scale applies Chinese National Standard (CNS) A4 specification (21〇X 297 public) --- 1328584

Obtaining the title compound as an off-white crystalline material according to the general method described in the example ίο, obtained by first reacting (buquinoline-based sulfoximin-4-yl)-sterol with sulfinium gas, and then Reaction with 2·ethylimidazole and sodium hydride followed by chromatography and crystallization of the hydrochloride. Melting point &gt; i25t: cleavage (ethyl acetate/hexane), MS: m/e = 290 (M+H+). Example 221 Ethyl-imidazolium-hydrazide-capped carbazate··carbazole·Meal 1&lt;; Qin Jin Obtained the title compound as an off-white crystalline material according to the general method described in Example 10, which was obtained by first use (1) _Porphyrin_6_yl·1H_imidazole_4_yl)-methanol is reacted with sulfinium gas, and then reacted with 2-ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Hyun point &gt; 7 9 〇c decomposition (ethyl acetate / hexane), MS: m / e = 304 (M + H +) » Example 222 g_^f4-(2-mercapto- -1-ylmethyl咕 sniffing a certain ~|g杳' said that the title compound was obtained as an off-white crystalline material according to the general method described in Example 10, which was obtained by first using porphyrin _8_yl·1Η·imidazole-4·yl)- Methanol is reacted with sulfinium gas and then reacted with 2·ethylimidazole and sodium hydride, followed by chromatography and crystallization of the hydrochloride. Refining point 15〇_154〇C (ethyl acetate / hexane), MS: m/e = 290 (M+H+). Example 223 ?-Γ4-(2-ethyl-imidazol-1-ylmethylimidazole-1-yl 1 崦 崦 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵 遵First use (1_„奎啦_8_基-1Η_imidazol-4-yl)-methanol to react with sulfinium chloride, then with 2_ethylimidazole and hydrogen•104- this 尺度-scale common Chinese national standard (CNS ) Α 4 specifications (210Χ 297 mm) 1328584

The sodium reaction is followed by chromatography and crystallization of the hydrochloride salt, with a bright spot of 78_8 丨.匸 (ethyl acetate / hexane) ' MS: m/e = 3 04 (M+H+). Example 224 L-(l-benzopyrene, 31 氲 氲 ; -5-yl-exo-oxazol-4-one methyl, "H-leaf _ 2-ylamine hydrochloride pound Π: 2) Follow the example 104. The general method, 1Η-imidazole, ΐ_[[ι·(13_benzodioxan-5-yl)-1Η-imidazole-4-yl]methyl]-2-nitro- and iron Acetylene reaction. After filtration, evaporation and chromatography, the title compound free base was isolated. The free base was converted to its pale yellow hydrochloride "melting point &gt; 245 ° C decomposition (decyl alcohol / diethyl ether), MS: m / e = 284 (M + H +). Example 225 Difluoromethyl hydrazine _4·fluoro-phenyl)-5-(2·methyl hydrazine-imidazole·1·yl carbazide was given the title compound according to Example 129 (DMF instead of dioxane, 4 hours, 1 〇 〇 ° C) is a light brown solid (73 〇 / 〇), which is prepared via 2_(3_difluoromethyl_4_fluoro-phenyl)-4,4,5,5-tetramethyl-[1 , 3,2]dioxadiborazine and 3_bromo-5-(2-indolyl- 0-sal-1-ylindenyl)-!; prepared by a bite reaction. MS: m/e = 318.3 ( M+H+) Example 226 Difluoro-ethyl)-phenyl1-5-(2·曱某-q卡地]·Methyl^Biha title compound according to Example 129 (DMF replaces two-burn, 4 H, 1〇〇C) is an aged brown solid (70%) prepared by [2_(3_(1,1-difluoroethyl)-epi]-4,4,5,5-tetramethyl -[1,3,2]dioxathiamidine and 3bromo-5_(2_methyl·sodium sulphate) were prepared by a bite reaction. MS· m/e=3l4 3 (M +H+). -105- This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm)

k 1328584 A7 B7 Five inventions description (1〇2, · Example 227. 3-(3-Ga-5-trismethyl-phenyl)-5-(2-methyl-weiling-i-ylmethyl The title compound was light brown (67%) according to Example 129 (DMF for k 2, 4 hours, 100 C). The preparation was via 2-(3-fluoro-5-trifluoromethyl). Benzo)-4,4,5,5-tetradecyl-[1,3,2]dioxanthene and 3_-___________methyl-methane-1 -ylmethyl) _Ρ ratio bite reaction to prepare eMS: m/e=336.3 (M+H+) ο Example 228 1: L3-(1,1-difluoro-ethyl)-4-fluoro-stupid 1-5-C2-methyl -Miso-U-methyl)-pyridine compound was light brown solid (73 〇 / 〇) according to Example 129 (0 117 instead of two s, 4 hours, ι〇〇β〇) -[3-(1,1·difluoroethyl)_4_fluoro_phenyl]·4,4,5,5-tetramethyl-[1,3,2]dioxadiboron and 3 _ _ _ 5 _ ( 2 曱 - 咪 咪 咪 -1- 曱 曱 曱 ) - - - ι ι ι 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 229 229 229 229 229 229 229 U U U U Cyclopropyl-1-indole "1-(3,4-dioxime 1 methyl 1' according to the general method described in Example 1 'The title compound was obtained via 4_ gas methyl-1-(3,4 -Dichloro- The title compound was obtained as a yellow oil. MS: m/e = </RTI> (M+H+) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Example 23'0 5-(4-Fluoro-3-methyl-phenyl)-1-methyl-2-(2-methyl------------------------------------ Chinese National Standard (CNS> 八四规+格(210乂297 mm)· 1328584 A7 B7 V. Description of Invention (103) Imidazole hydrochloride Π : η 5-bromo-1-indenyl-2-(2- Mercapto-imidazole-methyl-methyl)·1Η-imidazole (01 g, 0.392 mmol) was dissolved in terpene (4 ml) and methanol (8 ml), aqueous 2 Ν sodium carbonate (0.2 mL), 4-Fluoro-3-mercaptophenyl dihydroxyboric acid (0.078 g, 0.510 mmol) and hydrazine (triphenylphosphine) palladium (23 g, 〇〇 2 〇 millimolar). It was refluxed under argon for 12 hours, then cooled to room temperature and dried over sodium sulfate. After the solvent was removed by filtration and evaporation, the residue was chromatographed, eluted with dioxane / decyl alcohol = 95:5. In methanol, cooled to 〇 ° c and treated with hydrochloric acid / ether "evaporation to remove solvent and at a high degree The title compound (0.11 g, 88%) as a pale yellow solid dehydrated. MS: m/e = 285.2 (M+H+) 〇 Example 23 1 fluoro-3-trifluoromethyl- succinyl hydrazine -methyl _2·(2·methyl-imidazole a•基甲)-1Η- Imidazole salt 醅鲤p : 1) 5-bromo-1-indenyl-2-(2-indolyl-imidazolium-i-ylindenyl)_1H-imidazole (01 g, 0.392 mmol) dissolved in DMF (1.5 ML), with potassium carbonate (〇1 g, 〇784 mM), 2-(4-fluoro-3-trifluoromethyl-phenyl)·4,4,5,5-tetradecyl-[1 ,3,2] Dioxazolidine borane (0.148 g, 0.510 mmol) and hydrazine (triphenylphosphine) (0.047 g, 〇_〇 40 mmol) treatment of the reaction mixture m10〇〇c Heated under argon for 12 hours' then cooled to room temperature and dehydrated with sodium sulfate. After removal of the solvent by filtration and evaporation, the residue was purified (jjjjjd The product was dissolved in decyl alcohol and cooled to hydrazine. It is treated with hydrochloric acid/ether. The solvent was removed by evaporation <RTI ID=0.0></RTI> to <RTI ID=0.0> MS: m/e = 339.2 (M + H +).

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Example 232. Zhi Er (4-gas-3-dimethyl-methyl)-1-mercapto-2-(2-methyl-flavored [•基甲)-1Η-imidazole hydrochloride pound Π:遵 According to the general method described in κ, Example 2 3 1 , the compound is derived from 1-methyl-2- 2 (2-methylimidazol-1-ylmethyl)-1 Η-imidazole and 2-(4-gas- 3-Mercapto-phenyl)· 4,4,5,5-tetradecyl-[1,3,2]-dioxene was obtained. Ms: m/e=300.1 (M+). Example 233 M-Methyl-imidazol-1-ylindenyl)-pyridin-3-yl 1-L2.3 4-tetrahydro-dano. Hydrochloride (1:2) This compound was prepared according to the schematic procedure described in the following references: S. Wagaw; SL Buchwald; Journal of Organic Chemistry 1996, 61, 7240-7241 3-bromo-5-(2-methyl Methyl-1-methyl-methyl)·Ρ比 bite (〇.1 g, 0.397 mmol) dissolved in toluene (1 ml), continuous use of 1,2,3,4-tetrahydroisoindoline (61 Microliter, 0.476 mmol; 'Third sodium butoxide (53 mg, 0.556 mmol), Pd2(dba)3 gas-like complex (8.2 mg, 0.0079 mmol) and R(+)-BINAP (10 mg, 0.0159 mmol) treated. The reaction mixture was at 70. The crucible was heated under argon for 6 hours, cooled to room temperature and quenched with water. The aqueous layer was extracted three times with ethyl acetate. The combined extracts were dehydrated with sodium silicate, filtered and the solvent removed in vacuo. The residue was chromatographed (gelatin) eluted with dioxane / methanol = 95:05. The product was dissolved in methanol, cooled to 0 ° C and treated with hydrochloric acid / ether. The solvent was removed by evaporation and dehydrated under high vacuum to give the title compound (yield: 9 g, 60%) as yellow foam. MS: m/e = 305.3 (M+H+). -108- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm)

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1328584 A7 B7 V. INSTRUCTIONS (105) Example of a method for preparing an intermediate 234 1^(3,4-di-environment·mum ym-imidazole-4-oxo acid 3,4-dimethanolamine (24.3 g, 150 Milligram), a mixture of triethyl orthoformate (24.0 g, 162 mmol), ethyl nitroacetate (2 〇 〇 ,, 150 mmol) and ethyl acetate (1 mL) was refluxed for 1 hour. After adding an additional amount of ruthenium citrate (300 ml, 1.8 m), iron powder (450 ml), and acetic acid (3 ml, 5.2 m), the mixture was refluxed for 5 hours. During this period, an additional amount of iron powder (25.1 g, 450 mmol) was added in 3 portions. The mixture was cooled to 6 〇 eC and ethyl acetate (1 liter) was added. After refluxing for 1 min, the precipitate was filtered and the filtrate was concentrated. The residual acetic acid was removed by azeotropic distillation with co-evaporation with toluene (500 ml). The crystalline residue was dissolved in dioxane (300 ml), 2N sodium hydroxide solution (300 ml) and charcoal (about 10 g) were added. The mixture was refluxed for 2 hours, filtered and cooled to 5 °C. A hydrochloric acid solution (3 7%) was added until the precipitation was completed. Filtration and drying gave the title compound (25.8 g, 67%). Melting point &gt; 235 ° C Decomposition (water), MS: m/e = 255 [(M-Η)·]. Examples 235 to 262 were prepared according to the general procedure described in Example 2:34. Example 235 W4-argon-3-methyl-phenyl-V1H-imidazole-4-furoic acid title compound MS: m/e = 236 (M+), melting point 231-236 ° C (water / bis) Obtained as an off-white crystalline material obtained by reacting 4-ox-3-methylaniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthoacetate 'iron and acetic acid And subsequent hydrolytic hydrolysis. Example 236 -109- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 Five A7 _____ B7 Invention Description (1Q6) 1-四鱼. 辟-5-某-lH-piH斗· 4-heteroic acid title compound MS: m/e = 227 [(M-Η)·], melting point 243·25 Γ (: (water / ban) is obtained as an off-white crystalline material obtained by 5-amine The tetrahydrogen imprint is reacted with the original formic acid diethyl acetonate, the nitric acid ethyl acetate and the acetic acid, followed by treatment with diethyl ortho ruthenate, iron and acetic acid and subsequent aqueous hydrolysis. Example 237 丄二(3,4 - monomethyl-bens)-1Η-p-tox-4-cyanic acid title compound MS: m/e = 216 (M+), melting point &gt; 250. (: (water/dioxane) is grayish white crystal Substance acquisition is obtained by reacting 3,4-diphenylaniline with triethyl orthosilicate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid, and subsequent Analytical hydrolysis. Example 23 8 1-P. quinone-1H-imidazole-4-brewed title compound MS: m/e=2〇2 (M+), melting point &gt;25〇°C (DMF) is a rose color Acquired crystalline material The mode is carried out by reacting p-toluidine with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid, followed by alkaline hydrolysis. Example 239 _1·(4- Fluoro-3-methyl·melly)-1Η-carbazole-4-# acid title compound MS: m/e=219 [(M-Η)-), melting point 192-198 Χ: (water / dioxane Is obtained as an off-white crystalline material obtained by reacting 4·fluoro-3-indolylamine with triethyl orthoformate, ethyl nitroacetate and acetic acid, followed by triethyl orthosilicate, Iron and acetic acid treatment followed by prophylactic hydrolysis β Example 240 • 110- This paper scale applies to China National Standard (CNS) Α 4 size (210X297 mm)

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1-(4-Mercaptothiopyranyl-stupyl-upm-salt-4-heteroic acid title compound MS: m/e=233 [(MH)·], melting point 233-245. (:(水/二咩作:) is obtained as a red crystalline material obtained by reacting 4_(mercaptothio)aniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by diethyl proruthenate 'iron and acetic acid Treatment and subsequent pro-hydrolysis. Example 241 1-(3-Trifluoromethyl phenyl sulfonium-4-carboxylate title compound MS: m/e = 256 M+, m.p. 233-245. The alkane is obtained as a light-colored crystalline material obtained by reacting 3-(trifluoromethyl)aniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by triethyl orthosilicate , iron and acetic acid treatment and subsequent alkaline hydrolysis. Example 242 1-(4-Fluoro-3-trifluoromethyl-miao)-1Η·Bole ol-4-xiang g妾 title compound MS: m/e= 274 M+, melting point 188-193. (: (water/dioxane) is obtained as an off-white crystalline material obtained by 4-fluoro-3-(trifluoromethyl)aniline and triethyl orthophthalate, Ethyl nitroacetate and acetic acid are reacted Treatment with triethyl orthoacetate, iron and acetic acid followed by alkaline hydrolysis. Example 243 1-(3-Fluoro-4-trifluoromethyl-methyl)-1Η-imidazole-4-carboxylic acid title compound MS: m/e = 274 M+, melting point &gt; 25 (TC (water/dioxane) is obtained as an off-white crystalline material obtained by 3-fluoro-4-(trifluoromethyl)aniline and the original hydrazine. Triethyl ethoxide, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. • 111 · This paper scale applies to the Chinese National Standard (CNS) A4 specification ( 210 X 297 mm)

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1328584 A7 B7 V. INSTRUCTIONS (108) EXAMPLE 244. λ·ΐ(4-_Methyl-3-trifluoromethyl-benzomh-yttrium-4-thin title compound MS: m/e=269 [(M-Η)·), melting point &gt; 233. (: decomposition (water/dioxane) is obtained as an off-white crystalline material obtained by 4_mercapto-3-(difluoromethyl)aniline with triethyl orthoacetate, ethyl nitroacetate, And acetic acid reaction, followed by treatment with triethyl orthoacetate, iron and acetic acid followed by prophylactic hydrolysis. Example 245 1-(4-gas-3-helium-mosa V1H-oxazol-4-跆醅 heading Compound MS: m/e = 252 (M+), m.p. 231-236. 〇 (water/dioxane) is obtained as a light red crystalline material. The obtained method is obtained by gas 3-methoxyantamine and orthoformic acid. Ethyl ester, ethyl nitroacetate, and acetic acid are reacted, followed by treatment with triethyl orthoformate, iron and acetic acid followed by an exemplary hydrolysis. Example 246 h (4-Fluoro-3-trimethyl-methyl)-1Η - oxazole-4-oxime title compound MS: m/e = 236 (M+), melting point &gt; 182. (: Decomposition (water/dioxane) is obtained as a light brown crystalline material obtained by way of 4 _ Fluorine_3_nonoxyaniline is reacted with triethyl orthosilicate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid followed by alkaline hydrolysis. Chloro-3-methyl-mum)-1Η-imidazole-4-indole title compound MS: m/e=222 (M+), melting point &gt;250*t(水/二》院) The color crystalline material is obtained by the reaction of 4-aniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by the use of the original hydrazine.

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1328584 A7 ____B7 V. INSTRUCTIONS (109) Treatment with triethyl acid, iron and acetic acid followed by alkaline hydrolysis. Example 248 JL-Bist and hydrazine 1.31-dihydro-indole-5-an-1H-imidazole-4-free oxime title compound MS: m/e = 232 (M+), mp. (: (water/dioxane) is obtained as a gray crystalline material obtained by reacting 3,4-decylenedioxyaniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by use Treatment with triethyl orthoacetate, iron and acetic acid followed by alkaline hydrolysis. Example 249 1-(3-Ga-4-methylindole-indenyl)-1Η-wazole-4-carboxyindole The title compound MS: m /e=220 (M+), melting point &gt;250eC (water/di 1^ yard) is obtained as an off-white crystalline material obtained by 3-fluoro-4-mercaptoaniline and triethyl orthosilicate Ethyl nitroacetate, and acetic acid are reacted, followed by treatment with triethyl orthoacetate, iron and acetic acid followed by an assay of hydrolysis. Example 250 1-(3- Argon-4-methylr-yl)-1Η-哚The title compound of the azole-4-carboxylic acid MS: m/e = 252 (M + )' The melting point of 224-226 ° C (water / ii 1 ^ 院) is obtained as a white crystalline material, which is obtained by means of 3-gas _4_methoxyaniline is reacted with triethyl orthoformate 'acetic acid ethyl acetate, and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. Example 251 1-(4- Gas-2-gas-stupid) -1 Η-味 sn sn-4-cyanic acid title compound MS: m / e = 239 [(MH)-], melting point 234-2381^1^/: 4 alkane) is obtained as a pale yellow crystalline material, obtained by Reaction with 4-chloro-2-fluoroaniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by -113- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 _ B7 V. INSTRUCTION DESCRIPTION (110) Treatment with triethyl orthosilicate, iron and acetic acid followed by alkaline hydrolysis Example 252 1-(4-Bromo-indole azole-4-carboxylic acid title compound MS : m/e = 266 (M+), melting point &gt; 250 ° C (water / dioxane) is obtained as a pale yellow crystalline material obtained by 4-bromoaniline and triethyl orthosilicate, nitro Ethyl acetate, and acetic acid are reacted, followed by treatment with triethyl orthoacetate, iron and acetic acid followed by basic hydrolysis. Example 253 Difluoromethane-methyl V1H-imidazole·4·decanoic acid title compound MS: m /e=253 [(Μ-Η)-], m.p. 218-225. 〇(water/dihydroalkane) is obtained as a white crystalline material obtained by 4-difluoromethoxylamine and ortho-decanoic acid. Sanyi S, Xiao The acetic acid, and acetic acid are reacted, followed by treatment with triethyl orthoformate, iron and acetic acid followed by an experimental hydrolysis. Example 254] - (4 - lower base gas - presently based) - 1 Η -11 to 嗤 - 4 The title compound MS: m/e = 293 [(Μ-Η)·], melting point 238-243 Τ: decomposition (water / No. 2) is obtained as an off-white crystalline material obtained by 4-benzyloxy The stilbene is reacted with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. Example 255 1 ΐ(3-methoxy-4-indolyl-styl)·ιη-味喷-4-Acidic acid The title compound MS: m/e = 232 (Μ+), mp 226-230. (: (water/dioxane) is obtained as a rose-colored crystalline material, which is obtained by means of 3_曱氧_4_曱

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1328584 A7 ________B7 _._ V. Description of the invention (111) The reaction of a phenylamine with triethyl orthoformate, ethyl nitroacetate, and acetic acid followed by treatment with triethyl orthoformate, iron and acetic acid followed by alkali Sexual hydrolysis. Example 256 _1-(4-Trifluoromethyl-Benzene-Saliva-4-cyanate title compound MS: m/e = 256 (M+), melting point &gt; 250 ° C (water / two 1 ^ hospital) Obtained as a pale yellow crystalline material obtained by reacting 4-(trifluoromethyl)aniline with triethyl orthoformate, ethyl nitroacetate' and acetic acid, followed by triethyl orthoacetate, iron and acetic acid Treatment and subsequent alkaline hydrolysis. Example 257 1-(1,3-digas·iso-stuppy#-5-V1H-&quot;--4-carboxylic acid title compound MS: m/e=230 (Μ +)' Melting point 245-247 ° C (DMF / water) is obtained as a light brown crystalline material obtained by means of 3 · dihydro 5 5 isophthalonitrile (according to TY Shen et al., Journal of Medicinal Chemistry) , 1987, 7JL 965 preparation) is reacted with triethyl orthosilicate, ethyl nitroacetate, and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid followed by alkaline hydrolysis. Example 258 1-( 4-Fluoro-3-indolyl sulphate V1H-carbazole-4-indole S. The title compound MS: m/e = 236 (M+), melting point &gt; 182 ° C decomposition (water / dioxane) is shallow Obtained as a brown crystalline material obtained by 4_fluoro_3 The amine is reacted with dibasic acid diacetate, nitroacetic acid ethyl acetate, and acetic acid, followed by treatment with formic acid diethyl acetonate, iron and acetic acid, followed by prophylactic hydrolysis. Example 259 -115- This paper scale applies to China National Standard (CNS) A4 Specification (210X 297 mm) 1328584 A7 _ B7 V. Description of Invention (112) Phenyl-1H-indole-4-carboxylic acid title compound MS: m/e=188 (M+)' The melting point of 220-221 ° C (DMF / water) is obtained as a white crystalline material obtained by reacting aniline with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by triethyl orthosilicate, Iron and acetic acid treatment and subsequent alkaline hydrolysis. Example 260 1-(4·A-argon-Cym-V1H-imidazole-4-carboxylic acid title compound MS: m/e = 218 (M+), melting point &gt; 240 ° C (water/dioxane) is obtained as a light brown crystalline material obtained by reacting p-anisidine with triethyl orthoformate, ethyl nitroacetate, and acetic acid, followed by triethyl orthoformate, iron and Acetic acid treatment followed by alkaline hydrolysis. Example 261 1-(3-Methylhydrazine-Momot)-1Η-Imidazole-4-carboxylic acid title complex MS: m/e = 218 (M+), melting point 196-201 ° C (water / hexane) obtained as a light red crystalline material obtained by the intermediate anisidine and triethyl orthophthalate, Ethyl nitroacetate and acetic acid are reacted, followed by treatment with triethyl orthoformate, iron and acetic acid followed by a prophylactic hydrolysis. Example 262 1-(4-Oxyl-3-trifluoromethyl-phenyl)-1 oxime-imidazole-4-indole The title compound MS: m/e = 286 (M+), mp. (: Decomposition (water/dioxane) is obtained as a light brown crystalline material obtained by 4-methoxy-3-(trifluoromethyl) phenylamine and triethyl orthoformate, ethyl nitroacetate. And acetic acid reaction' followed by treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. -116- This paper scale applies to China National Standard (CNS) A4 specification (210X 297 public)

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Example 263.2 bis(3,4·dioxybenzoquinone)-5·methazine diimidazole imidazole _4_carboxylic acid ethyl ester and di-milk-phenyl)-5-methyl-3H-°dox-4 - ethyl orthoacetate 3,4-diphenylphenyldihydroxyboronic acid (8 22 g, 43" mmol), ethyl 4-mercaptoimidazolecarboxylate (6.64 g, 43.1 mmol) and copper acetate ( 11) (7 83 g, 43 mM) in a suspension of dioxane (86 mL) was stirred at 2 EtOAc for 48 hours. The whole solid was removed by filtration, and the organic phase was diluted with ethyl acetate (500 ml) and stirred with a sat. After filtration and evaporation, the residue was purified by chromatography (EtOAc eluting eluting elut 3H·^azole ice resorcinating ethyl vinegar [spot 135-136 ° C (ethyl acetate / hexane) 'MS: m / e = 298 (M +)] and 10 g (8%) 1- (3, 4 - 二气-笨基)_5 -曱基·ΐΗ-°米唾-4-缓酸乙酷 [ Hyun Point 163-164°C (ethyl acetate/hexel), MS: m/e=298 (Μ +)]. Example 264 1-(3,4-digas-jamma V1H-imidol-4-yl 1-methylxene^(3,4-dichlorophenyl)-1Η-imidazole-4-carboxylic acid (20_0 g, 77.8 mmol; treated with 1 Μ BH3 THF complex (100 mL) and reflux for 2 hr. The mixture was cooled to 5 ° C and decyl alcohol (20 mL) was slowly added. After evaporation of all volatiles, the residue was taken up in 2N. Hydrochloric acid solution (1 ml) and reflux for 2 hours. After hot water, the hot water phase was slowly treated with 2N sodium hydroxide solution to pH 1. The title compound crystals as white (12.2 g, 65%). 〇c (water), MS: m/e = 242 (M+). Examples 265 to 292 were prepared according to the general procedure described in Example 264. Examples 265 -117 This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) A7 B7 V. Inventive Note (114) U bis(4-oxo-3-t^phenyl)_1H-imidazole Xue title σ, MS: m/e=222 (Μ+), Hyun Point 126_i33eC (water) is obtained as a light brown crystalline material obtained by reacting 1(4_gas_3_methyl-phenyl)·1Η-imidazole·4-carboxylic acid with BA THF complex followed by Subsequent hydrolysis treatment. 266 II-Tetrahydroindole·5-yl-1H-imidazole·4·Reaching — title compound, MS: m/e = 214 (Μ+), melting point 128-133. (: (water) is light brown Obtained as a crystalline material obtained by reacting tetrahydrofuran-5-yl-1H-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis followed by example 267 dimethyl-mum)-1Η- Carbazole _4_1·1 gas title compound, MS: m/e = 202 (M+), melting point 11 〇 _116. 〇 (water) is obtained as an off-white crystalline material obtained by 1 _(3 , 4_Dimercapto-phenyl)-1H-imidazole-4-carboxylic acid is reacted with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 268 p-Methylyl-1H-indazol-4-ylmethanol title compound , MS: m/e = 188 (M+), melting point i〇ll 〇 2 ° C (water) is obtained as an off-white crystalline material, which is obtained by 1-pair 曱 基 一 一 啥 啥 啥 4-carboxylic acid The reaction with BH3 THF complex followed by hydrolysis followed up. Example 269

Ubii-Fluor-3-A-Laughter V1H-Imidazole-4-Mercapto-118. 1328584 A7 B7 V. Description of Invention (115) Title Compound, MS: m/e=206 (M+),. The melting point of 13 8-144 ° C (water) is obtained as an off-white crystalline material obtained by the method of 1-(4-fluoro-3-methyl-phenyl)-1H-imidazole-4-carboxylic acid and BH3 THF. The compound reaction is followed by hydrolysis followed up. Example 270 "1-(4-Methylsulfanyl-styl-V1H-imidazol-4-yl-methanol-title compound, MS: m/e = 220 (M + ), m.p. It is obtained as a light brown crystalline material obtained by reacting 1-(4-methylsulfanyl-phenyl)-1H-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis for subsequent treatment. 271 Γΐ-(3-Trifluoromethyl-phenyl V1H-imidazol-4-yl 1-methanol title compound, MS_m/e=242 ( Μ+), melting point 96-100 ° C (water) as white crystal Substance obtained obtained by reacting 1-(3-trifluorodecyl-phenyl)-1H-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 272 Γ 1-(4 -Fluoro-3-trifluoromethyl-p-styl)-1 -imidazolyl-4-ylpropanol title compound, MS: m/e = 260 (M + ), mp 142-146 ° C (water) The crystalline material is obtained in a manner that is obtained by reacting 1-(4-fluoro-3-trifluoromethyl-phenyl)-1 -imidazole-4-carboxylic acid with a BH3 THF complex followed by hydrolysis for subsequent treatment. 『1-(3-Fluoro-4-trifluoromethyl-jamma V1H-imidazol-4-yl 1-nonanol-119- This paper scale applies to China Standard (CNS) A4 size (210X 297 mm) stapling

1328584

The title compound 'MS: m/e = 260 (M+) m. (: (water) is obtained as a white crystalline material obtained by reacting 1-(3-fluoro-4-trifluoromethyl-phenyl)-1Η-imidazole-4-carboxylic acid with BH3 THF complex. Subsequent water subsequent treatment. Example 274 Γ.1:(4-_£·基曱某笑V1H•carbazole-4·^Ί•甲醢 Title compound, MS: m/e=257 (Μ+Η+ ), melting point 116-1193⁄4 (water) is obtained as a white crystalline material's obtained by 1-(4-mercapto-3-trimethylsulfonylphenyl)-1Η-imidazole-4-carboxylic acid and BH3 The THF complex reaction followed by hydrolysis followed up. Example 275 Π-(4-oxo.: 3-oxime-mum)·1Η-indazol-4-yl-1·carbazide title compound 'MS: m/e =23 8 (Μ+) 'Melting point 116-119t (water) obtained from white crystalline material obtained by 1-(4-carb-3-oxo-phenyl)-1H-imidazole-4-carboxylate The acid is reacted with the BHs THF complex followed by hydrolysis for subsequent treatment. Example 276 Π-(4-Fluoro-3-methyl argon-loaded with a V1H-xanthene-4-one-methyl-title compound, MS: m/e = 222 (Μ+), melting point 174-177 ° C (water) obtained as an off-white crystalline material obtained by 1-(4-fluoro-3-indolyl-phenyl)-1 - Imidazole-4-carboxylic acid is reacted with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 277 Γ1-(4-Gas-Bud V1H-Imidazol-4-yl 1-methanol _ 120- This paper scale applies to China Standard (CNS) A4 specification (210X297 mm)

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1328584 A7 B7

The title compound 'MS: m/e = i 〇 8 (M+), melting point 115-116. The hydrazine (acetonitrile acetate) is obtained as a white crystalline material obtained by the reaction of 1-(4- gas-phenyl 1H-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis followed. Example 278 ' The title compound is MS3 m/e=218 (M+), and the grafting point is 150-157°C (water). The white crystalline material was obtained by the reaction of benzodioxolan-5-yl-1H-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis followed up. Example 279 [1-(3- Fluor-4-methyl-M-V1H-imidazol-4-yl-l-methyl-title compound, MS: m/e=206 (M+), m.p. 115-122. (: (water) is a pale yellow crystalline material. Obtained, obtained by reacting ip-fluoro-4-indolyl-phenyl)-1Η-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 280 [1-(3- gas -4-Methane-supported)-1Η-oxazol-4-yl 1-methylindole title compound, MS: m/e = 238 (M+), mp 133-138X: (water) obtained as an off-white crystalline material Obtained by 1_(3-Ga-4-oxo-phenyl)-1H-imidazole-4-carboxylic acid with BH3 THF The complex reaction followed by hydrolysis followed up. Example 281 Γ 1-(4-Ga-2-Gas-Methyl)-1Η-imidazole-4-early A_ -121 - This paper scale applies to Chinese National Standard (CNS) A4 Specifications (210 X 297 public)

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Line 1328584 A7 B7 V. Description of the Invention (118) The title compound, MS: m/e = 226 (M+), mp 120-130 ° C (water) obtained as an off-white crystalline material obtained by 1-( 4-Vethyl-2-fluoro-phenyl)-1H-imidazole-4-carboxylic acid is reacted with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 282 [1-(4-Bromo-phenyl)-111-imidazol-4-yl 1-methanol title compound, m.p. The yellow crystalline material is obtained by the reaction of 1-(4-bromo-phenyl)-1Η-imidazole-4-carboxylic acid with a BH3 THF complex followed by hydrolysis for subsequent treatment. Example 283 Γ1-Μ-二气甲莫V1H-imidazol-4-yl 1-methylxyl title compound, MS: m/e=240 (M+), mp 66-72 ° C (water) as light brown crystal The material is obtained in a manner that is obtained by reacting 1-(4-difluoroindolyl-phenyl)-1H-imidazole-4-carboxylic acid with a BH3 THF complex followed by hydrolysis for subsequent treatment. Example 284 Γ 1-(4-Mercapto-m-yl)-1 oxime-imidazol-4-yl-methanol mp mp m m m m m It is obtained as a white crystalline material obtained by reacting 1-(4-mercaptooxy-phenyl)-1Η-imidazole-4-carboxylic acid with a BH3 THF complex followed by hydrolysis for subsequent treatment. Example 285 Γ1-Π-Methane-4-methyl-methyl)-1Η-imidazol-4-yl 1-methanol title compound, m.p. ) is -122- This paper scale applies to China National Standard (CNS) A4 specification (210X 297 mm) 1328584 A7 B7 Five inventions description (119 white crystalline material obtained, obtained by i_(3-methoxy-4) - mercapto-phenyl)-1H-imidazole-4_carboxylic acid is reacted with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 286 LLI4-trimethyl-methyl-methyl)-ιη·咣基μ甲醢Compound, MS: m/e = 242 (Μ +), melting point 153-156 Χ: (water) obtained as an off-white crystalline material obtained by 1-(4-trifluoromethyl-phenyl)·1Η-imidazole The 4-carboxylic acid is reacted with a BA THF complex followed by a subsequent treatment with hydrolysis. Example 287 [1-(1,3-dioxin-iso-and-bito-5-m)-1!^-°m-sodium-4-one-methanol title compound 'MS: m/e=216 (Μ +), melting point 161-165. (: (ethyl acetate) is obtained as an off-white crystalline material obtained by the method of 1_(1,3·dihydro-isobenzofuran-5-yl)-1Η-imidazole-4-carboxylic acid and BH3 THF. The </ br> </ br> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 120 ° C (dichlorohydrazine / diisopropyl ether) is obtained as a white crystalline material obtained by (4-fluoro-3-methoxy-phenyl)·1Η-imidazole-4-carboxylic acid and BH3 THF complex reaction followed by hydrolysis for subsequent treatment. Example 289 (1-Methyl-1H-imidazol-4-yl V-carboxamide title compound 'MS: m/e = 174 (M+), mp. Water) is -123- This paper is suitable for Chinese National Standard (CNS) A4 specification (210X297 mm) 1328584 A7 B7 V. Invention Description White crystalline material obtained 'its obtained by phenyl_1Η·ο米峻_ 4_ Carboxylic acid is reacted with BHbTHF complex followed by hydrolysis for subsequent treatment. Example 290 Γ1-(4-methoxy-jamma sal-4-a 1-methylxyl title compound 'MS: m/e=204 (M+) , melting point i〇7-l〇9°C (ethyl acetate) The white crystalline material was obtained as 'obtained by the reaction of 1_(4_曱-oxy-phenyl)-1H·. m.sup.4-carboxylic acid and BH3 THF complex followed by hydrolysis followed up. Example 291 『1- (3-methylhydrazine-stupidyl imidazole-4-one 1-methylindole title compound 'MS: m/e=204 (M+), mp 80-85T: (ethyl acetate / hex···) The obtained method was obtained by reacting 1_(3_oxa-phenyl)-1Η-imidazole-4-carboxylic acid with BH3 THF complex followed by hydrolysis for subsequent treatment. Example 292 Π-(4-oxo-3 -Trifluoromethyl-stupyl-mythracene-4-one-1. The title compound, MS: m/e = 272 (M+) 'melting point 147-150X: (water) is obtained as an off-white crystalline material. The reaction is carried out by reacting 1 _(4_methoxy = gas thiol-phenyl)-1 Η-miso-4-carboxylic acid with BH3 THF complex followed by hydrolysis. Example 293 Π-(3·gas-4 -Methyl-Zipyl)-1 H·Saliva-4·yl~|·A-side according to Example 234' 3-Chloro-4-methyl-p-amine (21.5 g, 150 mmol) with triethyl orthoformate Ester, ethyl nitroacetate and acetic acid are reacted, followed by the use of the original ruthenium tris-124-

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k This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1328584 A7 ___ B7 V. Description of invention (121) ' &quot; Ethyl, iron and acetic acid treatment and subsequent. Hydrophilic hydrolysis. The isolated acid (10.0 g) was purified directly from EtOAc EtOAc (EtOAc) Melting point 126-133 ° C (ethyl acetate / hexane), MS: m / e = 222 (M+). Examples 294 through 297 were prepared according to the general procedure described in Example 293. Example 294 Π-(4-Ga-3-trifluoromethyl-stupid)-1 -°米 sn sn-4-a~|-methylxyl-3-trifluoromethyl-4-aniline and orthoformic acid The triethyl ester 'nitroacetate and acetic acid are reacted, followed by treatment with triethyl orthoformate, iron and acetic acid, and then basic hydrolysis. The isolated acid is directly purified using BH3 THF </RTI> </ RTI> </ RTI> </ RTI> followed by hydrolysis to give the title compound, m.p. 148-153 <RTIgt; , a white crystalline solid. Example 295

Ll-(3-chloro-4-fluoro-jam-1Η-_吨-4-yl-1·methanol 3-aluminum-4-aniline with triethyl orthoformate, ethyl nitroacetate and acetic acid' Treatment with triethyl orthoacetate, iron and acetic acid, and subsequent acceptance of the analytical hydrolysis. The isolated acid is directly reduced with BH3 THF complex followed by hydrolysis to give the title compound, m.p. e = 226 (M+), as an off-white crystalline solid. Example 296 (_1-Co-B-4--M-Methanol 4-phenylphenylamine was reacted with triethyl orthanoate, ethyl nitroacetate and acetic acid, - 125- Paper &amp; degree ia_ g target standard (CNS) M specification ( tender 297 public)

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K-1328584 A7 ------- B7 V. INSTRUCTION DESCRIPTION (122) Subsequent treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. The isolated acid was directly purified using a BH3 THF complex, followed by hydrolysis to give the title compound, m.p. (: (dioxane/diisopropyl ether), MS: m/e = 250 (M+), as a yellow crystalline solid. Example 297 isopropyl hydrazol-3-methyl-m. 1-methylxyl-4-isopropyl-3-methyl-phenylamine is reacted with triethyl orthoacetate 'nitroacetic acid and acetic acid' followed by treatment with triethyl orthosilicate, iron and acetic acid, and subsequently The acid which was subjected to basic hydrolysis and hydrazine separation was directly purified using BH3 THF complex' followed by hydrolysis to give the title compound, m.p. 98-1 〇 2 C (yield/diisopropyl), MS: m /e=230 (M+), as a yellow crystalline solid. Example 298

Li-(3,4-diindole-Vinyl)-5-methyl-1H-imidazole-4-some 1-methylindole in 1-(3,4-dioxa-phenyl)·5-fluorenyl- iH-° meters. A solution of 4-deoxyethyl ester (0.82 g, 2.7 mmol) in THF (27 mL) was added portionwise to EtOAc (0.21 g &lt;RTIgt; The mixture was stirred in an ice bath for 2 hours' then slowly added 1 ml of a saturated sodium salt solution. After diluting with 100 ml of ethyl acetate, the mixture was filtered, concentrated and chromatographed eluted with EtOAc EtOAc (EtOAc:EtOAc The title compound was obtained as a white crystalline solid (0.46 g, 6%). Hyun point 174-17 5 ° C (dioxane / diisopropyl ether), MS: m / e = 256 (M +). Example 299 4-gas fluorenyl-1-(3.4·di-argon-smiling V1H-imidazole•126- This paper scale applies to gg family (CMS) A4 specification (21Q X 297 public) 1328584 A7 B7 V. Invention Description (123) Slowly add sulfinamide (39.5 ml, excess 4-dichloro-phenyl)-111-° m--4-yl]-methanol (9,6 g, 39.5 mmol) in an ice bath. The resulting mixture was stirred for 24 hours. After evaporation, the oily residue was triturated with ether to give 1 g (yield: 86%) of the title compound hydrochloride as an off white solid. The mixture was neutralized with EtOAc. , MS: m/e = 260 (M+). Example 3 0 0 m-imidazole, 1-indole 1-(3,4-diphenyl)-iH-oxazol-4-one 1 Azza 9-Saki 4- 4-methylmethyl-1-(3,4-dichlorophenyl)-lH-imidazole (2.0 g, 7.5 mmol) dissolved in DMF (25 mL) - 2-nitroimidazole (1 加入) Grams, 8.8 millimoles) and barium carbonate (1.43 grams, 4.4 millimoles), the result The mixture was stirred at 7 ° C for 3 hours. After evaporation of the solvent, the residue was crystallised eluted eluted eluted eluted Obtained to 50% (di-methane/methanol = 9:1) eluted to yield 2 48 g (98%) of the title compound as pale white solid. mp. /e=291 [(MN〇2)+]. Example 301 11^-°10, 啥' gas _3·methyl phenyl)_1H-imidazole _4_篡1 nitro group - according to example 299 [1 -(4-Chloro-3-methyl-phenyl)_1H•imidazole_4_ylbupropanol is reacted with sulfinium gas to obtain 4-gas sulfhydryl-helium anal gas_3·methyl_stupyl) ·1Η_咪

1328584 A7 ________B7 _ V. Description of the invention (124) 嗤 Further direct reaction with its hydrochloride. Thus as described in Example 300, '4-azepine-1-(4-a-3-methyl-phenyl).1Η-imidazole hydrochloride with 2-nitroimidazole (1.2 equivalents) and carbonic acid planer (1.2) Equivalent) reaction, after evaporation and subsequent purification of the extract, results in the crude product obtained, which is purified by chromatography. Melting point 147-148 ° C (dioxane / hexane), MS: m / e = 271 [(Μ - Ν〇 2) Ί. Examples 302 and 303 were prepared according to the general procedure described in Example 301. Example 302 1 -Imidazole '1-"丨1-(4-Methyl-Mo)-1 -Imidazole-4-, 1 曱1-2-indolyl-(1-p-tolyl-1Η-imidazole The -4-yl)-methanol was first treated with sulfinium and then with 2-nitroimidazole and cesium carbonate. The title compound was obtained as a white solid after evaporation, workup, and chromatography. Hyun point 147-148 ° C (dioxane / diisopropyl ether), MS: m / e = 23 7 [(MN 〇 2) +] » Example 303 1H-imidazole, 2-nitro-1- K1-methyl-1H-carbazol-4-yl)methyl 1-(Phenyl-1H-imidazol-4-yl)-nonanol was firstly sulfinated with sulfinium and then 2-nitroimidazole and carbonic acid planer deal with. The title compound was obtained as a white solid after evaporation, EtOAc. Melting point 126-127. (:(dioxane/diisopropyl ether), MS: m/e = 223 [(M-N02)+]. Example 3 04 1-(3,4-di-p-phenyl)-1 Η -Miso-4-pot acid nectar carbonyl diimidazole (0.49 g '3 mmol) added to ι_(3,4-dioxaphenyl)-indole-imidazole-4-carboxylic acid (0.64 g '2.5 The mixture was stirred in DMF (10 mL). After 1 hour at 60 ° C, the reaction mixture was cooled to room temperature, aqueous ammonia (25%, 20 mL) was added and stirring was continued for 12 hours. Then add water (100 -128- This paper size applies to Chinese National Standard (CNS) A4 size (210X297 mm) B7 V. Invention instructions (125 ml) 'Filter out the precipitated product. Recrystallize from ethanol to give the title compound as off-white crystal Melting point 244-245 ° C (ethanol), MS: m/e = 255 (M+). Example 305 Dioxane-studyl ViH-imidazole-4-methyl-n-methyl fumarate π:1\ 1- (3,4-Di-O-phenyl)-indole-imidazole-4-acidic decylamine (4.32 g, 16-9 mmol) was treated with 1 Μ BH3 THF (100 mL) and reflux for 6 hours. Cool to 5 ° C and slowly add decyl alcohol (50 ml). After evaporation to remove all volatiles, The residue was taken up in 6N aqueous HCl (30 mL) and refluxed for 15 min. The reaction mixture was subjected to &lt;RTI ID=0.0&gt;&&&&&&&&&&&&& Sodium sulphate), concentrated, and the obtained crude product was purified by chromatography (dichloromethane / hexane / hydr. Substance (2.62 g '64%). The title compound was isolated as a white crystalline material after EtOAc (m.p.). 241 (M+). Example 306 N-"l-(3,4-digas-phenyl)-1Η-imidazole-4-yl-methyl-1-acetamide in 1-(3,4-dioxane Phenyl)-1Η-imidazole-4-decylamine (0.20 g, 0-83 mmol). To a solution of THF (30 mL), triethylamine (0 079 g, 0.78 mmol) and acetonitrile ( The residue was dissolved in ethyl acetate and washed with water. The crude product was chromatographed eluting with EtOAc EtOAc (EtOAc:EtOAc) »熔-129· The paper scale applies to China@家标准(CNS) A4 specification (210X297 mm) 1328584 A7 ___ B7 i, invention description (126) ~ point 177-180 °C (methanol / dichlorinated sputum), MS: m/e = 284 (M+H+). Example 307

Nd:l-(3,4-dioxo-phenyl)-1Η-imidazole-methyl]-indole N-[l-(3,4-di-phenyl)-1Η-imidazole- 4·Base-methyl-acetamide Q] g, 3.7 mmoles, added Lawesson's reagent (0.82 g, 2.0) in a suspension of 1,2-dimethoxyethane (11 ml). Millions) and the mixture was refluxed for 90 minutes. After adding saturated sodium hydrogencarbonate solution (50 ml) and extracting with dioxane (3 χ 100 ml), the combined organic phases were dried (sodium sulfate) and concentrated, and the obtained crude product was chromatographed Gas decane to 1 〇〇 0 / 〇 (diqi methane / decyl alcohol = 9: 1) elution] «The title compound was obtained as a brown crystalline material ( 〇 75 g, 68%). Melting point 166-17 (TC (methanol / dioxane), MS: m / e = 299 (M +). Example 308 1 Π Π - (3, 4- dioxo-phenyl) _iH - imi. - 曱 early hh-h to jun-2-jiayu 4-chloroindolyl-l-(3,4-dichloro-phenyl)-1 Η-imidazole (1 31 g '5.0 mmol) dissolved in DMF ( 10 ml), 2·imidazole carboxaldehyde (〇48 g, 5 〇 mmol) and carbonic acid planer (0.82 g, 2.5 mmol) were added, and the resulting mixture was stirred for 12 hours under evaporation. The residue is dissolved in ethyl acetate and washed with water. The organic phase is dried (sodium sulfate), concentrated and chromatographed eluted eluted eluted elut The title compound was obtained as an off-white solid, m.p. 13 </ s </ s </ s </ </ </ </ > </ </ </ > </ </ > </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Always two Jr-based)-3-methyl-1H-pyrazole and 〗 π.4-Di-argon-芏D-5-

1328584 A7 B7 V. INSTRUCTIONS (127) A solution of mercapto-1H-pyrazole 3,4-dichlorophenylhydrazine (4.27 g, 20.0 mmol) in ethanol (5 mL) and water (50 mL) Treatment with 3-oxybutyraldehyde didecyl acetal (2.64 g, 20.0 mmol) and reflux for 1 hour. The alcohol was removed in vacuo and the aqueous residue was taken ethyl acetate (2 X 150 mL). The organic phase was dehydrated (sodium sulfate), filtered and evaporated. The residual oil was purified by chromatography [[J], eluting with gradient hexane to 1 〇〇 /0 (hexane / ethyl acetate = 1:1) to obtain 3.01 g ( 66%) 1-(3,4-dioxa-phenyl)-3-methyl-1H-pyrazole [melting point 57-58 ° C (ethyl acetate / hexane), MS: m / e = 226 ( M+)] is off-white crystals and 1.32 g (29%) of 1-(3,4-di-phenyl)-5-methyl-1H-pyrazole [melting point 46-47 ° C (hexanes) 'MS: m/e = 226 (M+)] is a white crystal. Example 310 Chloromethyl-l-[3,4-dioxa-phenyl]-1Η-pyridinium 1-(3,4-dioxa-phenyl)-1Η-pyrazole-4-carboxylic acid (3.0 g , 12 mmol (US 5064851) was treated with 1 M BH3 THF (50 mL) and refluxed for 90 min. The mixture was cooled to 5 ° C and methanol (50 mL) was slowly added. After evaporation of all volatiles, the residue was taken up in 25% hydrochloric acid (50 mL) and reflux for 15 min. After filtration, the aqueous phase was cooled in an ice bath and slowly treated with a 28% aqueous solution of sodium hydride (50 mL). The title compound was obtained as a pale yellow material (2.6 g, 86%). Melting point 66-67 ° C (water), MS: m/e = 260 (M+). Example 3 11 1-(3.4-Bis-Methyl)-1Η-pyrazole-4·carbaldehyde [1-(3,4-di-phenyl)-1Η-imidazol-4-yl]-nonanol ( 10.8 g, 44.3 mmol) solution of a mixture of THF (270 ml) and water (30 ml) using manganese oxide • 131 - This paper scale applies to the gg standard (CNS) A4 specification (21Q 297 297 public)

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k 1328584 A7 B7 V. INSTRUCTIONS (128) -- (IV) (5 g '57.5 mmol) treatment, the mixture was refluxed for 4 hours. A second portion of oxidized (IV) (1.5 g) was added and reflux was continued for 1.5 hours. The mixture was filtered through Celite and the residue was washed with methanol. Toluene was added to the filtrate, and the water was removed by distillation. The brown residue was taken up in the second gas, and white crystals were formed upon standing. 1-(3,4-di-phenyl-phenyl)-1&gt;{-° miloxime-4-brewing (2.5 g, 25%), MS: m/e = 240.0 (M+) 〇 Example 312 1- Π- (3,4-diqi-stupyl V1H-miso-4-yl 1-ethanol in methyl iodide in ether (3 Μ, 13 _7 ml, 41.1 mmol) and ether (40 ml) was added in portions to 1-(3,4-di-phenyl-phenyl)-indolyl-4-imidazole-4-carbaldehyde (2.58 g, 10.7 mmol). Then slowly added THF (50 mL) Stirring under reflux for 1 hour. After adding aqueous ammonium hydride (saturated, 3 mL), the mixture was extracted with ethyl acetate. The organic phase was dried (sodium sulfate) and evaporated to give 1-(3,4·2 gas -Phenyl)-1Η-imidazol-4-yl]-ethanol (2.56 g, 93%) as a light brown solid. MS: m/e=257.0 (Μ+Η+). Example 313 1-(3,4- Diqi-laughing)-iH-imidazole-4-free methyl ester 1-(3,4-di-phenyl)_1H-imidazole-4-carboxylic acid (7.0 g, 27 mmol), sterol A mixture of (150 ml) and concentrated sulfuric acid (25 ml) was refluxed for 3 hours. Then the solution was concentrated to about 80 ml, and sodium carbonate (60 g) was added to a solution of water (500 ml). The title compound (6.0 g, 81%) was obtained as a pale brown solid. MS: m/e=269.9 (M+). 314 _____ ·132· This paper is suitable for towel sg family (CNS) Α4 specifications (9) (four) 97 public love) 1328584 A7 ___ B7 V. Invention description (129) 2-『1-(3,4-二气-苯某) _1^-嵘崦-4- a 1-indol-2-ol in the same manner as in Example 312, i_(3,4-di-phenyl)-1Η-imidazole-4,carboxylate (1.5 g, 5.53 millimolar) treated with excess mercapto magnesium iodide. The title compound (1.3 g, 86%). m. Example 315 1H-imidazole, 2-anthracene (2-methylindole-1H-imidazole-1-yl)methyl1-4-anthracene 3-(single) phenyl1-1-anthracene 2-(trimium) Ethylene acetophenone 1-methyl 1_ 1 Η-imidazole ' 4-iodo-2-[(2-mercapto-1 Η-imidazol-1-yl) fluorenyl] 1-[[2-(tridecyldecane) Ethyl]methyl-(0.080 g, 0.191 mmol) dissolved in toluene (4 ml) and methanol (0.8 ml) with 2 Ν sodium carbonate (0.2 ml), 3-(trifluoromethyl)benzene Treatment with bishydroxyboronic acid (0.049 g '0.248 mmol) and hydrazine (triphenylphosphine) palladium (0.0114 g, 0.0095 mmol). The reaction mixture was refluxed under argon for 150 hours' then cooled and dried (sodium sulfate) at room temperature. After the solvent was removed by filtration and evaporated, m~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ e=437.4 (M+H+). Examples 3 16 to 3 19 were prepared according to the general procedure described in Example 3 15. Example 316 jjl dimethicin, 4-(4-fluoro-3-indolylphenyl)-2-indole (2-methylimidazole), methyl hydrazine-hydrazine 2-(trimethyl decyl) ethyl argon 1A, the title compound 'MS·· m/e=400.2 (Μ+) is from 1Η-imidazole, 4·iodine·2·[(2-methyl-1Η-imidazol-1-yl)indenyl]- Preparation of 1-[[2-(tridecylidenealkyl)ethoxy]indolyl- and 4-fluoro-3-indolylphenyldihydroxyboronic acid. •133.

1328584 A7 __ ____B7 V. Description of Invention (13Q~) — -- Example 3 17 .1H-1嗔' 4-(3,4-Di.fluoro-benzoquinonemethyl_1H-imidazole] a) A VI-丨丨2-(Trimethyldecyl)ethane ethane oxime ^ Title compound, MS: m/e = 404.2 (M+) from 1H-imidazole, 4-iodo-2-[(2-methyl-1H- Imidazolyl-1-yl)indolyl]trimethylsulfonylalkyl)ethoxy]indolyl- and 3,4-dimethylmethyldicarboxylate are prepared by the acid. Example 3 18 1. Technique-Electric scent 2-|~(2-甲啥二卜基)甲Μ-Γ4]甲某益,笑基1-1-172-(三methyl石夕烧基)ethoxy 1_ The title compound, MS·· m/e = 414_2 (Μ+) is from 1Η-imidazole, 4-iodo-2-[(2-methyl-1H-imidazol-1-yl)methyl]trimethylnonane Preparation of ethoxy] fluorenyl- and 4-methylthiophenyldihydroxyboronic acid. Example 3 19 1 Η-座 4-(4-Fluoro-3-methylphenyl)_2_Γ1Η_imidazolylmethyl V1_ Γ[2-(trimethyldecyl)hexidine]&gt; title compound 'MS: m /e=387.3 (Μ+Η+) is from 1Η-imidazole, 2-(1Η-味吐-1-ylindenyl)-4-iodo-indole-[[2·(trimethyldecyl)ethoxy] Preparation of methyl]• and 4·fluoro-3-mercaptophenyldihydroxyboronic acid. Example 320 1Η-味峻, 4-Moth-2-Γ(2-甲一-1Η-imidazol-1-yl)methyl1-1-"Γ2-(Pentylmethylalkyl)Ethyl 1A 1 - [4. Iodine-1-(2-(tridecylsulfenyl-ethoxycarbonyl)_1Η-imidazole·2·yl]methanol (1.0 g '2_8 mmol) and tetrabromodecane (13 g) , 4 〇 millimol) dissolved in THF (10.0 ml) and cooled to 〇〇c. Add 3 stupid-134 in 3 minutes. This paper scale applies to China's solid standard _ A4 specifications (21 〇 X297 公) 1328584 A7 _ B7 V. Description of the invention (131) phosphine (1.07 g, 3.95 mmol). The reaction mixture was stirred at 0 ° C for 1 hour to obtain a white suspension. In the second flask, sodium hydride ( 0.615 g, 14.1 mmol, 55% in mineral oil) suspended in DMF (20 mL) and cooled to 〇. 〇^ Partially added 2-methyl hydrazine (1.16 g, 14.1 mmol). 6 〇 〇 〇 〇 〇 〇 〇 〇 〇 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 Extract three times. The combined extracts are dehydrated with sodium sulfate. The solvent was removed in vacuo <RTI ID=0.0></RTI></RTI></RTI> <RTI ID=0.0></RTI> (M+H+) Example 321 was prepared according to the procedure outlined in Example 320. Example 321 1H-imidazole, 2-indole-imidazol-1-ylmethyl)-4-Moth-1-ΓΓ2-Γ三甲篡石夕A certain compound, MS: m/e = 405.3 (M+H+) is 4-bromo-1-(2-trimethylsulfanyl-ethoxycarbonyl)-1Η- Preparation of imidazol-2-yl]-nonanol and imidazole. Example 322 [1-Iodo-1-(2-trimethyldecyl-ethylchloromethyl)-iH-imidazole-2-some 1-methylindole 4-iodine 1-(2-trimethyldecyl-ethoxy)-iH-imidazole-2-carboxaldehyde (4.6 g ' 13.1 mmol) was dissolved in ethanol (5 mL) under argon. Sodium borohydride was added. (0.514 g '13.1 mmol), the mixture was stirred at room temperature for 45 min. Water (200 ml) was added and the aqueous layer was extracted with ethyl acetate three times. The combined extracts were dehydrated with sodium sulfate 'filtered and vacuumed' solvent The residue was taken up in hexane and stirred at room temperature to obtain [4-iodo 1-(2-trimethyldecyl-ethoxy) )- I_______ -135- This paper size is suitable for the standard (CNS) A4 specification (21〇&gt;&lt;297 public)- 1328584 A7 - _ B7 V. Invention description (132) 1H-imidazole_2_based] _ sterol (4. gram, 87%) was a white solid. MS: m/e = 354. 〇 (M+). Example 323 峨l峨-M2-trimethyl decyl-ethoxymethyl oxazolidine-2_methyl-5-diiodo-1-(2-tridecylfluorenyl-ethoxymethyl)·1Η-imidazole 8 86 g, 19.68 mmol) in anhydrous THF (110 mL) cooled to _78 ° &lt;3&gt; using n-butyllithium (13.5 mL '21.65 mM, 161 hexanes) The dropwise treatment was stirred at -78 ° C for 10 minutes and at -45. (After stirring for 30 minutes, the reaction mixture was cooled to -78 ° C and treated once with DMF (1 mL). The mixture was warmed to room temperature and saturated ammonium sulfate (1 50 mL) was added. The ester was extracted twice. The combined extracts were dried over sodium sulfate, and the solvent was evaporated, evaporated, mjjjjjjjj 18 g, 75%) light yellow oil "MS: m/e = 352.1 (M+). Example 324 4.5-diiodo-1-(2-trimethyldecane-ethyl-methyl)-1Η-哄岫4.5-Diiodo-imidazole (according to D_S. Carver, SD Lindell and EA Saville-Stones, tetrahedron, 1997, ϋ, 42, 14481-14496) Preparation (10·1 g, 31.6 mmol) was added portionwise to hydrogenation A suspension of sodium (1.38 g, 31.6 mmol, 55% in mineral oil) in anhydrous DMF (45 mL). The mixture was stirred at room temperature for 90 min then cooled to 〇 ° C and 2- Trimethylsulfonyl)-ethoxymethyl gas (6.81 ml, 34.7 mmol) was slowly treated in DMF (10 mmol). After stirring at 0 °C for 2 hours, the reaction mixture was poured. (200 mL) and ethyl acetate (50 ml) mixture "mixture was filtered, mother liquor present paper -136- acetate scale applies China National Standard (CNS) A4 size (210X297 mm) bookbinding

1328584 A7 B7 V. Description of the invention (133 ester extraction 3 times. The combined extracts are dehydrated with sodium sulfate, filtered and the solvent is removed in vacuo. The residue is purified by chromatography eluting with hexane/ethyl acetate = 9:1 The title compound (9-44 g, 66.4%) was obtained as pale yellow oil. MS: m/e=450.0 (M+). Example 325 3- chloromethyl-5-(3,4-dis a solution of [5-(3,4-di-phenyl)*^ butyl-3-yl]-methanol (4 70 mg, 1.9 mmol) and sulfinium chloride (4.9 ml) at 20 ° C After stirring for 15 hours, the sulfinium chloride was removed by evaporation and the title compound (558 mg, 98%) was obtained as a pale yellow solid. 326-328 was prepared according to the procedure outlined in Example 325. </RTI> </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> </RTI> <RTIgt; Obtained by reacting [4-(3 4-dioxa-benzoic)-pyridin-2-yl]-methanol with sulfinium chloride at 20 ° C for 15 hours, as a light brown foam (99% yield). Example 327 4-Methylmethyl-2-indole, 4-dichloro-molylpyridine hydrochloride title compound 'MS: m/ e=271.0 (M+) was obtained by reacting [2-(3,4-digas-benzoquinone)-mouth-battery-4-yl]-sterol with a subtle yield of 2〇C for 1 hour. Brown foam (1% yield). Example 328 3-Chloromethyl-5-(3,4-digas-jammidine hydrochloride (1:1^ title compound, MS: m/ e=245.1 (M+) is via [5-(3 4-diox-benzo-137-) paper scale applicable to China National Standard (CNS) A4 specification (210X297 public love) 1328584 A7 _ B7 V. Description of invention (134)) _2-Methyl-pyridin-3-yl]-methanol was reacted with sulfinium chloride at 20 ° C for 1 hour and then refluxed for 2 hours to give a yellow solid (98% yield). Example 329 Γ5-Γ3 .4-Dichloro-molylpyridine-3-mer 1-methanol in a suspension of lithium aluminum hydride (161 mg, 4.2 mmol) in THF (20 mL). 3,4-Di-O-phenyl)- nicotinic acid decyl ester (2.0 g, 7.0 mmol) in THF (20 mL), and then stirred at room temperature for 2 hr. 1) Quenching, then dehydrating directly with sodium sulfate, filtering and evaporating to remove the solvent. The residue is chromatographed [ruthenium, dioxane / (2M ammonia, decyl alcohol) = 97:3 Mention] to obtain the title compound (480 mg, 27%) as a orange solid. MS: m/e = 254.0 (M+H+). Examples 330-332 were prepared according to the general procedure described in Example 329. Example 330 Γ2-(3,4-di-p-pyridylpyridin-4-yl 1-methanol title compound, MS: m/e=252.0 ([ Μ-ΗΓ) was obtained as pale yellow solid (53% yield) It is obtained by reacting 2-(3,4-di-phenyl)-isonicotinic acid decyl ester with lithium aluminum hydride in THF at 20 ° C for 1 hour, followed by chromatography [gelatin, with dichloroguanidine Alkane/(2M-aminosterol)=19:1 elution]. Example 331 Γ4-Γ3.4-Dichloro-methylpyridin-2-yl 1-methanol title compound, MS: m/e=252.0 ([M -Η]·) is obtained as a light brown oil (94% yield) obtained by decyl 4-(3,4-di-phenyl)-pyridine-2-carboxylate and 1M aluminum hydride /THF solution was reacted in THF at 20 ° C for 1 hour, followed by chromatographic purification. ___- 138- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 B7 V. Description of invention (135 Example 332 ^^^~1^-stupid)-2-methyl-pyridin-3-yl 1^methanol hydrochloride pound gate.22 title compound,]^3:111/6=227.2 (1^+ ) is a ochre solid (5 8% yield) to be obtained by way of 5-(3,4-dimethyl-phenyl)-2-indenyl-ethyl acetate and sodium borohydride ( 5 equivalents) Ethanol (5 ml) was reacted and mixed for 2 hours at 2 Torr, followed by chromatographic purification. Example 333: chaotic phenyl) - acid oxime vinegar in 5-bromopyridine-3-carboxylate (2克, 9.3 mmol; 肆-(triphenylphosphine)-palladium (〇) (32 〇 mg '0.28 mmol) was added to a solution of hydrazine (50 ml) followed by lithium chloride (785 mg, 18.5 millimoles), the mixture is at 20. (: Stir for 30 minutes. Then add 3,4-dichlorophenyldihydroxyboronic acid (50% by weight in THF/water 9:1) (3.7 g, 3.3 ml, 9-7 mmol) and 2N aqueous potassium carbonate (11.3) </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; The title compound (2.48 g, 95%) was obtained as a pale solid. Ms: m/e = 281 </ </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> (M+H.) Examples 334-336 are according to the procedure outlined in Example 333. Example 334 4-(3, _4-di-methane-methyl-pyridin-2-carboxylate methyl ester title compound, MS: m/e=281.0 (M + ) is obtained by reacting 4-bromo-butan-2-carbazate with 3,4-dioxalyldihydroxyboronic acid, which is light yellow solid-139- This paper scale is applicable to China. National Standard (CNS) A4 specification (210X297 mm) 1328584

(10% yield). Example 335 diar arsenyl nicotinic nicotinamide title compound, MS: m/e = 281.0 (Μ+) via 2-iodo-isonicotinic acid 曱δ with 3,4-diphenyl The diboronic acid reaction gave 'light brown solid (59 〇 / 〇 yield). Example 336 ^ιί3,4-dioxadiylpyridin-2-carbamic acid methyl ester title compound, MS: m/e=282.0 (M+) via 6-bromo-pyridine-2-carboxylic acid methyl ester and 3 The reaction was carried out by the reaction of '4-di-phenyl-dihydroxyboronic acid as a pale yellow solid (7% yield). Example 337 2_-Moth-Different 絵···································· The sodium was heated together for 6 hours, and after extraction and aqueous subsequent treatment, 2·iodo-isonicotinic acid (7.3 g, 92.4% yield) was obtained. This material was dissolved in THF (50 mL) using EtOAc (EtOAc: EtOAc) The solvent was evaporated to dryness eluted EtOAcqqqqqqqqq MS: m/e = 263.0 (M+). Example 338 U odor-5-(2-mercapto-imidazole·ι_yl-methyl-pyridinium in sodium hydride (0.54 g '12·3 mmol) in THF (40 mL) at 20 ° C with stirring Add 2-mercaptoimidazole in several portions over 45 minutes in the liquid.

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This paper scale applies to China National Standard (CNS) A* specification (21〇χ 297 mm) 1328584 V. Invention description (137) After adding 3-Mo-5-(gas 曱 base)·ρ ratio bite (1 g, 4. Immol) in ethanol (8 mL), the mixture was heated under reflux for 1 hour under argon. After the solvent was removed by cooling and evaporation, the residue was suspended in methanol, filtered and then applied to silica gel. The title compound (0 56 g, 53%) was obtained as a yellow oil. MS: m/e = 251.0 (M+). Example 339 3-Bromo-5- (a gas methylpyridine in sulfinium chloride (41 mL, 344 mmol) in a cold solution in hydrazine. 〇 Care (highly exothermic) was added in portions (5 -&gt; σ 咬 -3- ) ) 曱 曱 曱 曱 曱 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 The title compound (9.1 g, 84%) was obtained as a pale-yellow solid. mp. m/e = 206.9 (M+). Example 340 (j-bromo-pyridine-3-methanolate 醴p::) 5·Bromonicotinic acid ethyl ester (25 g of '108 mmol) dissolved in ethanol (500 ml) at 20 °C The fresh sodium borohydride (25 g, 660 mmol) was added portionwise over 30 minutes. The mixture was continuously stirred overnight under an argon atmosphere. Thereafter, 1N hydrochloric acid (50 mL) was added slowly (after 2 min). 2N sodium hydroxide (25 ml) and water (75 ml) were added, and the mixture was stirred at ambient temperature for 2 hours. After evaporation to remove the alcohol, the aqueous phase was di-methane (4 x 150 ml) After extraction, the combined extracts were washed with brine and then dehydrated with sodium sulfate 'filtered and evaporated. The obtained yellow oil was dissolved in a small amount of ethanol and treated with 0.93 hydrazine hydrochloride/ethanol (62 ml of '1.2 equivalents) at 4 ° C for 1 hour. Removal of solvent and high vacuum dehydration at 5 ° C. 16 1328584 A7 B7 r V. Description of the invention (138 hours later, the title compound (1 〇 9 g, 44%) was obtained as pale yellow solid. MS: m/e = 186.9 (M+) 〇Example 341 1- i3,4-Dimercapto-mosyl)_2• formazan sulphonic acid ethyl ester was obtained from [3-didecylamino 2_2 (3,4·didecyl) _Phenyl)allylidine]-dimethyl-ammonium tetrafluoroborate (1:1), which is further composed of 3,4-didecyl-phenylacetic acid (according to aj Liepa; Australian Chemical Journal, 198H (12) ), prepared by 2647_55). Example 342 2_-ί4-gas-3-trifluoromethyl-phenyl&gt;)_4,4,5,5·tetramethyl _π 3 21 diborane borane Reference is made to a known method (γ. Masuda, Μ. Murata, S. Watanabe, Journal of Organic Chemistry, 1997, ϋ 6458-9). Contains potassium acetate (3.4 g '34.7 mmol), PdCl2 (PPh3) 2 (234 mg '0.34 mmol) and ι (pinac〇iato) two butterflies (32 g, 12' A 7 mM flask was charged with 5-bromo-2-a-p- and trifluoro (3 g, 11.5 mmol) in dioxane. The mixture was added to 10 ° C for 3 hours under an argon atmosphere. After cooling, ethyl acetate was added, and then the organic mixture was washed with a saturated sodium carbonate solution. The residue was purified by EtOAcjjjjjjjjj MS: m/e = 306.1 (M+). Examples 343-347 were prepared according to the general procedure described in Example 342. Example 343 2-(3,4-Ga-4-methyl-lamo)-4.4,5,5-tetradecyl-Γ1.3.21 Diargon-boron Boron-142- This paper scale applies to Chinese national standards ( CNS) A4 specification (210 X 297 兮 love)

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The title compound, MS: m/e = 252.1 (M+), was obtained as the starting material using 2- gas _4_ moth-toluene as a light yellow semi-solid (30% yield 344 hi4·oxy_3·methyl -phenyl)-4,4,5,5·tetramethyl hydrazine gas, 标题, the title compound, MS: m/e=252.1 (M+) obtained using 5_ desert_2_chloro_methyl stupid Colorless solid (16% yield). Example 345 5-(4,4,5,5-Tetramethyl-indole 1,3,21-dioxaindole borane·2_,-9,3-di- succinylfuran title compound, MS: m/e = 246.1 (Μ+) was obtained using 2,3-dihydro-5-bromobenzo[b]furan as a pale yellow oil (5 1% yield). Example 346 2·tetrahydroindole-5 -4,4,5,5-tetramethyl-indole 1,3,21-diindole, borax, the title compound, MS: m/e = 244.1 (M+) using trifluoro-decane Obtained as a light yellow oil (96% yield), and trifluoro-indene acid tetrahydroindole-5-yl ester is obtained from tetrahydroindol-5-ol. It was obtained by treatment with trifluoro-decanesulfonic anhydride, DMAP and triethylamine in dichloromethane at -70 ° C to 20 ° C. Example 347 2-(4-fluoro-3-trifluoromethyl-phenyl -4,4,5,5-tetramethyl-"1,3,21 dioxane borane title compound, MS: m/e = 290.1 (M+) using 5-bromo-2-fluoro- Obtained as benzotrifluoride as a colorless oil (76% yield). Example 348 -143- This paper scale applies to China National Standard (CNS) A4 specification (210X 297 mm) 1328584 V. Description of invention (14〇) Π -(3-trioxothiol-styl)·ιη_ρ米p sit-·4-base 1-methanol The general procedure of Example 293, 3 - (trifluoromethylsulfonyl) phenanthrene was reacted with diethyl decanoate 'nitroacetic acid and acetic acid' followed by treatment with triacetic acid, iron and acetic acid. Alkaline hydrolysis. The isolated acid was directly reduced according to Example 264. The reduction method was obtained by reacting with BH3 THF complex followed by hydrolysis and subsequent treatment to give the title compound as a light brown crystalline solid. H.s. 73-75 ° C (water). MS: m/e = 274 (M+). Example 349: difluoro-ethyl)-benzene. Dimer-ethyl)-aniline [R, 〇. Neri, JG Topliss, Ger. Offen. (1972), DE 2130452 19721221 CAN 78:124310] Reaction with triethyl orthoformate, ethyl nitroacetate and acetic acid' Subsequent treatment with triethyl orthoformate, iron and acetic acid followed by an analytical hydrolysis. The isolated acid was directly reduced according to Example 264. The title compound was obtained as a white crystalline solid. Melting point 1〇4-1〇8. 〇 (water), MS: m/e = 238 (M+). Example 350 {1-"3-(1,1-mono-ethyl-phenyl)-phenyl1-4-fluoro-1?-?m??-4-ylethanol followed the general procedure described in Example 293, 3-( 1,1_Difluoro-B tomb)_4_Fluorine-stupylamine is reacted with diethyl orthoformate 'nitroacetate and acetic acid, followed by treatment with triethyl orthoacetate 'iron and acetic acid' followed by alkaline The acid obtained by hydrolysis of β is directly reduced according to the example 264, and the reduction method is carried out by reacting with the Βη3 THF complex followed by hydrolysis to obtain the title compound as a white crystalline solid. 144- This paper scale is applicable to the Chinese S standard (CNS) A4. Specifications (210X 297 public) 1328584 A7 _____ B7 _ V. Description of invention ((4) ) Body: MS: m/e=257 (M + H+). Example 3 5 1 3-Π, 1-Difluoro-BV V4 -Chloro-mosamine added palladium on carbon in a solution of 2-(1,1-difluoro-ethyl-p-fluoro-fluoro-bu-nitrobenzene (10.4 g, 50.6 mmol) in methanol (200 mL) 10%, 4 g), the resulting mixture was hydrogenated at 20 ° C for 2 hours. After removal of the catalyst by filtration, the solvent was evaporated to give the title compound as a semi-solid substance (8.5 g, 96%). MS: m/e=l 75 (M+) » Example 352 2-( 1,1-two - B-Fluorine_4 - Nitrogen-Methyl 1-(2-fluoro-5-nitro-phenyl)-ethanone (ι〇·8 g, 59.0 mmol) in diethylaminotrifluoride A solution of sulfur (15.5 ml, 118 mmol) was added to 50. (: stirring for 6 hours. The mixture was cooled in an ice-bath, and slowly added to ice-cold aqueous 2? sodium hydroxide solution (100 ml). After extraction with dioxane, The title compound was obtained as a dark brown oil (yield: EtOAc, EtOAc) m/e = 205 (Μ +). Example 353 1-(3-Isopropyl-p-styl- saliva-4-acid as described in Example 234, 3-isopropyl aniline and triethyl orthanoate The ester 'nitroacetic acid B is intended to be reacted with acetic acid' followed by the use of the original acid triethylene glycol, iron and acetic acid treatment followed by alkaline hydrolysis to obtain the title compound as a light brown crystalline solid. Melting point &gt; 122 ° C decomposition ( Water/dioxane. MS: m/e=231 (M + H+). Example 354 -145- This paper scale applies to Chinese National Standard (CNS) A4 size (210X297 mm) Binding

1328584 V. INSTRUCTIONS (142) Π-(3-Isopropyl-phenyl V1H-carbazole-4-yl group follows the general procedure described in Example 264, 1-(3-isopropyl-stupidylazole_4_ rebellion The acid was reacted with a BH3 THF complex. The title compound was obtained as a light brown crystalline solid. m.p. s. s. 2-Base-1H-^Salt-4·Acid acid 曱西2- 2-茶基二经领酸 (1·4 g, 8 mmol), 1H-Mimi _4_carboxylic acid vinegar (1.0 g , 8 mM) and a suspension of copper acetate (1.4 g, 8 mmol) in di-methane (20 mL) at 20 ° C for 24 hours. Add ethyl acetate (1 mL) And saturated aqueous sodium salt solution (50 ml), the mixture was stirred for another 2 hours. After separation, the organic phase was dehydrated (sodium sulfate), concentrated and chromatographed (yellow gel, dioxin &gt; / sterol = The title compound (0.49 g, 24%) was obtained as white crystals. m.p. 143- 144 s (ethyl acetate). MS·· m/e=252 (M+). Example 356 (1) -Ny-2-yl-1 Η-° odor-4-yl methanol according to the schematic method described in Example 298 Ι_荇·2_yl-1H-imidazole-4-carboxylic acid oxime ester is reacted with a hydrogenation clock, followed by hydrolysis followed up and chromatography to give the title compound as a light brown gum. MS: m/e = 225 (Μ+) » Example 357 Π-(3-Iso-4-fluoro-phenyl-stimulus _4·yl·]-methyl-elast according to the general procedure described in Example 293, 3_bromo-4·fluoro-moleamine (K s γ· Lau et al., Journal of Organic Chemistry, 1981, 46, 2280-6) and triethyl orthoformate, nitric acid scale gg standard (CNS) M specification (plus twisting public love) Binding • 146- 1328584 A7 _____B7 V. Description of the invention (143) The reaction of ethyl acetate and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid, followed by alkaline hydrolysis. The isolated acid is directly according to Example 264. The reduction 'reduction method is obtained by reacting with BH3 THF </ br> </ br> </ br> </ br> 1-(3-&gt;Smell-Stupid V1H-Smell-4-Acidic Acid Following the general procedure described in Example 234, 3-bromoaniline was reacted with triethyl orthanoate, ethyl nitroacetate and acetic acid, followed by Treated with triethyl orthoformate, iron and acetic acid, followed by basic hydrolysis to give the title compound as a light brown crystalline solid. m.p. 205-207 ° C (water / dioxane) MS: m/e = 267 (M -Η·). Example 359 Π-(3-bromo-prepared to a V1H-imidazol-4-yl 1-methanol according to the procedure outlined in Example 264, 1-(3-bromo-phenyl)-1 Η-imidazole-4-carboxylic acid and BH3 The THF complex was reacted, followed by hydrolysis for subsequent workup. The title compound was obtained as an off-white solid. MS: m/e = 253 ( Μ + Η + ). Example 360 Γΐ-(3-vinyl oxime- 篡 篡)-iH-imidazole 4-yl 1-methanol under argon atmosphere, [1-(3-bromo-phenyl)-1Η-imidazol-4-yl]-nonanol (3.0 g, 12 mmol) in DMF (90 mL) The solution was treated with PdCh(PPh3)2 (〇_87 g, 0.1 mmol) and vinyltributylstannane (4.1 g, 13 mmol). The resulting mixture was heated to 60 ° C for 8 hours. After evaporating to remove the solvent, the residue was stirred with ethyl acetate (60 mL) and aqueous 10% potassium chloride solution for 30 min. The organic phase was separated and the aqueous phase was extracted three times with ethyl acetate. 1____147- Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7

The combined phase was dehydrated (sodium sulphate) and concentrated and chromatographed eluted with EtOAc (EtOAc: EtOAc (EtOAc) , 51%). MS: m/e = 201 (M+H+). Example 361 [1-(3-cyclopropyl-methylpyrazole-4-yl-1-methylxene under argon atmosphere, [1-(3-vinyl-phenyl)-1Η-imidazole-4-yl) A mixture of methanol (〇.1 g, 0.5 mmol) in toluene (2 ml) continued to use diethyl (3.8 ml of 1.1 hexane in hexane, 4.2 mmol) and diiododecane. (6 6 g '25 mmol). The resulting mixture was stirred for 12 hours at 2 Torr. The precipitate was filtered off and combined with ethyl acetate and a saturated aqueous ammonium hydride solution for 30 minutes. Dehydrated (sodium sulphate) and EtOAc (EtOAc m. A solution of 5-nitroindole aldehyde (1.7 g '1 〇 millimolar) in dioxane (5 〇 ml) using diethylaminotrisulfide (1·8 ml '14 mmol) The mixture was stirred for 20 hours at 20 C. Then a saturated aqueous solution of sodium hydrogencarbonate (2 mL) was added and the mixture was stirred for 1 hour. The organic phase was separated, dried (sodium sulfate) and chromat. 1〇〇〇/0 (hexane/ Ethyl acetate = 3:1) eluted to give the title compound as a colorless oil (1. 4 g, 74%). MS: m/e = 191 ( Μ+). Example 363 3 - difluoromethyl-4-fluoro- Add 2-difluoromethyl-1-fluoro-4 slowly at 120 ° C in a mixture of amine hydrochloride (ι: π in powder (88.0 g, 1.58 mol) in acetic acid (500 ml) at 120 °C -Nitrobenzene (25.0 g, 131 mmol-148- This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1328584 A7

ear). Stirring was continued for 15 minutes after completion of the addition. The reaction mixture was cooled to 20*t, filtered and evaporated. The residue was stirred with ethyl acetate (1 liter), filtered, evaporated, EtOAcjjjjjjjjjjj Dark brown oil (15.11 g, 72%). The analytical samples were treated with hydrochloric acid and crystallized as white hydrochloride. Melting point &gt; 240 ° C decomposition (sterol / diethyl ether), MS: m / e = 161 (M +). Example 364 1-(3-Difluoromethyl-4-gas-phenyl MH-imidazole-4-carboxylic acid according to the procedure outlined in Example 234, 3-difluoromethyl-4-fluoroaniline and diethyl orthoformate The ester 'nitroacetic acid and acetic acid were reacted' followed by treatment with triethyl orthophthalate, iron and acetic acid. Subsequent hydrolysis was carried out to give the title compound as a light brown crystalline solid. mp. 247. /二哼院).MS: m/e=255 (M-Η-). Example 365 Γΐ-(3-Difluoromethyl-4-1-phenyl)-1Η-imidazole-4-some 1-A g| Following the general procedure described in Example 264, 1-(3-difluoromethyl-4-fluoro-phenyl)-1 oxime-imidazole-4-carboxylic acid was reacted with BH3 THF. The title compound was obtained as an off-white solid. 133-134 ° C (water). MS: m/e=242 (M+) ° Example 366 1-(3-methylsulfanyl-phenyl-V1H-imidazole-4- The carboxylic acid was reacted according to the general procedure described in Example 234, 3-(methylsulfanyl)amine and triethyl orthoformate's ethyl nitroacetate and acetic acid, followed by triethyl phthalic acid, iron and acetic acid. Subsequent Acceptance of Hydrolysis" to obtain the title compound in gray-149- paper size Applicable to China National Standard (CNS) A4 specification (21〇X 297 public) 1328584 A7 __B7_ V. Description of invention (146^~ 'Color crystalline solid. Melting point 190-192°C (water/dioxane). MS: m /e = 234 (Μ-Η·). Example 367 Γ1-Π-methylsulfanyl-stupyl V1H-indol-4-yl"-methanol as outlined in Example 264, 1-(3-A Reaction of the sulfhydryl-phenyl)-1 oxime-imidazole-4-carboxylic acid with a BH3 THF complex followed by hydrolysis to give the title compound as an off-white crystalline solid. mp. MS: m/e = 221 (M+H+). </RTI> </RTI> </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; </RTI> <RTIgt; Trifluoromethoxy)aniline is reacted with triethyl orthophthalate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid followed by alkaline hydrolysis to give the title compound as a gray crystalline solid. Melting point 173-175 ° C (water / dioxane). MS: m / e = 273 (M + H +). Example 369 Γ 1-Π - trifluoromethane - stupid) -1 - imidazole - 4 1-A_ Following the general procedure described in Example 264, 1-(3-trifluorooxo-benzene ) -IH- imidazole-4-carboxylic acid complexes are reacted with BH3 THF, followed by hydrolysis to accept the subsequent processing of the title compound is obtained an off-white crystalline solid .MS:. M / e = 258 (M +). Example 370 Γ1-Π-Chloro-Stupid V1H-Imidazol-4-yl 1-A. Following the general procedure described in Example 293, 3-aniline was reacted with triethyl orthophthalate, nitroacetic acid and acetic acid. Use original tannic acid triethyl vinegar, iron and B-150- This paper scale is applicable to China National Standard (CNS) A4 specification (210X297 mm) 1328584 A7 B7 V. Invention description (147) Acid treatment, followed by analytical hydrolysis . The isolated acid was directly reduced according to Example 264. The title compound was obtained as a pale white crystalline solid. Melting point 78-79 ° C (water)'. MS: m/e = 209 (M+). Example 371 1-Indole 3-iodo-momenyl-1 oxime-imidazole-4-carboxylic acid Following the general procedure described in Example 234, 3-iodoaniline was reacted with triethyl orthoformate 'nitroacetate and acetic acid, followed by Treatment with triethyl orthoformate, iron and acetic acid followed by alkaline hydrolysis. The title compound was obtained as an off-white crystalline solid. Melting point 229-230 ° C (water / dioxane). MS: m/e = 313 (M-Η·). Example 372: Π-Π-iodo-mosyl)-1 Η-imidazol-4-yl 1-methanol The general procedure described in Example 264, 1-(3-iodo-phenyl)-1 oxime-imidazole-4-carboxylic acid and The BH3 THF complex is reacted followed by a subsequent treatment with hydrolysis. The title compound was obtained as a yellow oil. MS: m/e = 301 (M+H+). Example 373 1-Gentium-Gas-5-trifluoromethyl-phenyl V1H-imidazole-4-carboxylic acid Following the general procedure described in Example 234, 3-fluoro-5-trifluoromethylaniline and triethyl orthanoate The ester, ethyl nitroacetate and acetic acid are reacted, followed by treatment with triethyl orthosilicate, iron and acetic acid followed by alkaline hydrolysis. The title compound was obtained as a white crystalline solid. Melting point &gt; 250 ° C (water / dioxane). MS: m/e = 273 (M-Η·). Example 374 Γ 1-(3-Fluoro-5-trifluoromethyl-phenylindole-imidazol-4-yl 1-nonanol-151 - This paper scale applies to Chinese National Standard (CNS) Α4 specification (210 X 297 PCT) 1328584 A7 B7 V. INSTRUCTIONS (148) Following the general procedure described in Example 264 '1-(3-Fluoro-5-trifluoromethyl-phenyl)-1Η-imidazole-4-carboxylic acid with BH3 THF The compound was reacted, followed by hydrolysis, to give the title compound as a white crystalline solid. mp 144 </ </ </RTI> <RTIgt; </RTI> <RTIgt; </RTI> (water). MS: m/e = 261 (M+H+). Example 375 Γ 1-(3-methyl-5 -Trifluoromethyl-styl V1H-imidazol-4-yl 1-methanol according to the general procedure described in Example 293, 3-methoxy-5-trifluoromethylaniline and triethyl orthoformate, ethyl nitroacetate And acetic acid reaction, followed by treatment with triethyl orthoformate, iron and acetic acid, followed by alkaline hydrolysis. The isolated acid was directly reduced according to Example 264. The reduction method was carried out by reacting with BH3 THF complex followed by hydrolysis followed by hydrolysis. The title compound was obtained as a light brown crystalline solid. m.p. s.: 134 - 134 C (water), MS: m / e = 272 ( Μ + ). Example 376 Π Π Π 第三 第三 第三 第三 笨 笨 笨 笨 笨 笨 基1-methanol compliance The general procedure of Example 293, 3-tert-butylaniline was reacted with triethyl orthoformate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid followed by basic hydrolysis. The isolated acid was directly reduced according to Example 264. The title compound was obtained as a colorless oil, m.p. -1-4-trimethylamine-tactic V1H-imidazole-4-carboxylic acid according to the general procedure described in Example 234, 3-chloro-5-(trifluoromethoxy)aniline and triethyl orthoformate, nitro Ethyl acetate and acetic acid are reacted, followed by the use of the original tannic acid tri-152- This paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm)

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Ethyl, iron and acetic acid treatments were subsequently subjected to alkaline hydrolysis. The title compound was obtained as a light brown crystalline solid. Melting point 230-23 TC (water / dioxane). MS: m/e = 305 (M-Η-). Example 378 "1-(3-gas 4-trifluoroanthracene-stupyl-methanol-4-yl 1-methanol according to the general procedure described in Example 264, i_(3_ gas_4-trifluoromethoxy-phenyl) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Example 379 1·(3-Difluoroindole-phenyl V1H-imidazole-4-#g was taken according to the general procedure described in Example 234, 3-(difluoromethoxy)aniline and triethyl orthophthalate' Ethyl nitroacetate and acetic acid are reacted, followed by treatment with triethyl orthoformate, iron and acetic acid 'subsequently subjected to basic hydrolysis. The title compound is obtained as a light brown crystalline solid. mp 190-191 ° C. MS: m/e = 253. Example 380 Γ 1-(3-difluoromethane-stupyl)-1 Η-imidazol-4-yl 1-carboxamidine according to the general procedure described in Example 264, 1-(3- The reaction of the difluorooxime-phenyl bastazide 4·carboxylic acid with the BH3 THF complex was followed by the subsequent work up to afford the title compound as a white crystalline solid. MS: m/e = 240 (M+). 381 『1-(3-Difluoromethyl-styl V1H-imidazole- 4- Some 1A According to the general method described in Example 293, 3-difluorodecylaniline (gE Wdght et al. -153- This paper scale applies to Chinese National Standard (CMS) A4 specification (210X 297 mm) 1328584 A7 B7 , invention description (15Q), the Journal of Medicinal Chemistry '1995, ϋ 49-57) reacted with triethyl orthoformate 'nitroacetate and acetic acid, followed by treatment with triethyl orthoformate 'iron and acetic acid, followed by Alkaline hydrolysis. The isolated acid was directly purified according to Example 264. The title compound was obtained as a light brown solid, m.p. Example 382 Γ1-Γ3-bromo-5-fluoro-jamo)-1 Η-imidazol-4-yl 1-methanol The procedure outlined in Example 293 '3-bromo-5-fluoroaniline (K. Yoshiizumi et al., Bioorganic medicinal chemical letter, 1998, soap 3397-3402) is reacted with triethyl orthosilicate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid, followed by alkaline hydrolysis. The acid obtained was directly reduced according to Example 264, and the reduction method was via a complex with BH3 THF. The title compound was obtained as a light brown solid. m.p. 134 - 13 <RTI ID=0.0></RTI> </RTI> <RTIgt; Difluoro-methane #[1,31二气伍园-5-yl)-1Η-imidazol-4-yl 1-nonanol followed the general procedure described in Example 293, 2,2-difluoro-benzo[1, 3] Dioxol-5-ylamine is reacted with triethyl orthophthalate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid, followed by alkaline hydrolysis. The isolated acid was directly reduced according to Example 264. The title compound was obtained as a light brown solid. Melting point 163-164 ° C (water), MS: m/e = 254 (M+). Example 384 -154- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 ------^____._ V. Invention description (151) 1-;»奎格林-2-yl-1H-P m-sodium-4-cyanate ethyl 2-amino porphyrin (10.0 g '69 mmol), triethyl orthoformate (14 〇 ml, excess), nitroacetic acid A mixture of ester (9.2 g, 69 mmol) and acetic acid (1 mL) was refluxed for 3 h. A mixture of acetic acid (14 ml) and iron powder (11 g, 208 mmol) was added and refluxed for 5 hours. During this time, 3 additional iron powders (6 g each, 208 mmol) were added and the mixture was cooled to 60 ° C and ethyl acetate (5 mL) was added. After refluxing for 10 minutes, the precipitate was filtered off and the filtrate was concentrated. The residual acetic acid and toluene (500 ml) were co-evaporated and removed by co-boiling. The title compound was obtained as an off-white crystalline material (12.2 g, 66%). Melting point 129-130. (: (ethyl acetate / hexane), MS: m / e = 268 (M + H +). Example 385 (1-ling 4-2-yl-114-°m °^-4-) - A Xue Following the general procedure described in Example 298, 1-, quinolin-2-yl-ih-[deg.]-4-oxo-indole 曱S was reacted with the hydrogenation chain followed by hydrolysis followed up and chromatography to obtain the title compound. Grayish white crystalline material. Melting point 136-137. 〇 (ethanol), MS: m/e = 225 (M+). Example 386 [1-(3- </ RTI> </ RTI> </ RTI> </ RTI>咄 篡 篡 篡 | | _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Treatment with triethyl orthoformate 'iron and acetic acid followed by basic hydrolysis. The isolated acid was directly reduced according to Example 264. The reduction was carried out by reacting with BH3 THF complex followed by hydrolysis and subsequent treatment. Brown crystal solid-155- 1328584 A7 _____?!_ V. Description of invention (152) - Body. Melting point 105-106 ° C (water), MS: m/e = 308 (M+). Example 387 Ι-p Kui Lin-3-yl-1H-spirt ton-4-cyanate ethyl vinegar according to the example 384 Briefly, the 2-amino porphyrin is reacted with triethylacetic acid formic acid, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid. After subsequent treatment and chromatography, the title compound is obtained. </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; -4- a solution of V-methyl 1- quinolin-3-yl-1H-imidazole-4-carboxylate (5_0 g, 18.7 mmol) in a suspension of toluene (1 mL) to -78 (: Add diisobutylaluminum hydride (19 ml of 1 M in THF, 19 mmol) while maintaining the temperature below _7 ° C. The mixture is stirred at this temperature for 2 hours, then the reaction mixture is allowed to slowly Arrive at 〇 ° C. Add saturated aqueous sodium salt solution (1 ml) and stir continuously. The mixture is diluted with ethyl acetate (100 ml), filtered, concentrated and chromatographed. Methane to 80% (dioxane / decyl alcohol / aqueous ammonium hydroxide = 90:10:1) eluted. The title compound was obtained as a light brown crystalline solid (12 gram ' 28%). 145. (: (ethyl acetate), MS: m/e = 226 (M+H+). Example 389 · 蚱b from -2 - yl 1H-bead 啥 竣 竣 竣 竣 遵 遵 遵 遵 遵The method, 2, amine _5_gas pyridine is reacted with triethyl orthoformate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthosilicate, iron and acetic acid. After the subsequent treatment and chromatography, the title compound was obtained. The paper size is applicable to the Chinese National Standard (CNS) Α4 specification (210X297 公爱〇 -156-1328584 A7)

'by the mouth of a crystalline solid. Hyun point 163-164 ° C (ethyl acetate), MS: m/e = 252 (M+H+). Example 390 Π-(5-Gas-pyridine-2-mer V1H.imidazole-4.yl 1-methanol according to the general procedure described in Example 388, ι ((5- chloro s </ br> -4_ Resin-ethyl acetoacetate is reacted with diisobutylaluminum hydride. After the hydrolysis treatment and chromatography, the title compound is obtained as a light brown crystalline solid. m.p. 82-87 ° C (ethyl acetate / ether), MS: m/ e=210 (M+H+). Example 391 1-Iso-Jin-3-yl-1H-Miso-Tetra-Tetraic Acid Ethyl Ethyl Ethyl Ethylacetate The reaction of triethyl sulphate, succinyl acetate and acetic acid was followed by treatment with triethyl ethane formic acid, iron and acetic acid. After subsequent workup and chromatography, the title compound was obtained as a crystalline solid. 162 ° C (ethyl acetate), MS·· m/e = 268 (M+H+). </RTI> </RTI> </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; Method, 1-isoquinolin-3-yl-1H-imidazole-4-methylate methyl ester is reacted with lithium aluminum hydride, followed by hydrolysis followed up and chromatography. The title compound is obtained as a pale white waxy solid. MS: m /e=226 (M+H+) Example 393 Π-(4-Trifluoro Methane-Mu V1H-carbazol-4-yl 1-methanol according to the general method described in Example 293, 4-(trifluoroanthracene)aniline and protoporic acid tri-157- This paper scale applies to the national standard of solid state (CNS) Α4 size (210 X 297 mm)

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K- V. Description of the Invention (154) The ethyl ester, ethyl nitroacetate and acetic acid are reacted, followed by treatment with triethylacetic acid formic acid, iron and acetic acid, followed by alkaline hydrolysis. The isolated acid was directly reduced according to Example 264, and the reduction was carried out by reaction with a BH3 THF complex followed by hydrolysis to give the title compound as a white crystalline material. Solvent point 105-106 ° C (diethyl ether), MS: m / e = 258 (M +) » Example 394 1-(4-tris-methylsulfanyl-phenyl)-1 Η-carbazole概略According to the general procedure described in Example 234, '4-(trifluoromethylsulfanyl)-phenylamine was reacted with triethyl orthoacetate 'nitroacetate and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid' Acceptive hydrolysis. The title compound was obtained as a light brown crystalline solid. Melting point 247-248. (:(水/二。号烧)》MS: m/e=288 (M+) » Example 395 Π-(4-Trifluorodecyl-alkane-stupyl)-1Η-oxazol-4-one 1- Methanol Following the general procedure described in Example 264, 1-(4-trifluoromethylsulfanyl-phenyl)·1H-imidazole-4-hypoacid was reacted with BH3 THF complex, followed by hydrolysis followed up. The compound is an off-white crystalline solid. M.p. 145-147. (: (water). MS: m/e = 275 (M+H+). Example 396 1-p---------- The acid-reducing vinegar was reacted according to the general procedure described in Example 384, and the 6-amino sulfonium was reacted with triethyl orthosilicate, ethyl nitroacetate and acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid. After the subsequent treatment and chromatography, the title compound was obtained as a brown crystalline solid. m.p.: 90-94 ° C (ethyl acetate/hexane), MS: -158- The paper size is applicable to the Chinese National Standard (CNS) A4 specification. (210X297 mm) 1328584 V. Description of invention (155 m/e=268 (M+H+) Example 397 + (l-^»Quin p-L-6-yl-lH-ball sniffing 4-V-Methanol compliance example The general method of 388, 1 · porphyrin-6-yl-1H-imidazole-4-carboxylic acid ethyl ester and diisobutyl hydrogen The title compound was obtained as a light brown crystalline solid. m.p. 183-187 ° C (ethyl acetate /hexane). MS: m/e=226 (M+H+) Example 398 l-tr-quile-8-yl-1H-imida-4-propionic acid ethyl ester according to the general procedure described in Example 384, 8-amino morpholine and triethyl orthosilicate, nitroacetic acid The ester is reacted with acetic acid, followed by treatment with triethyl orthoformate, iron and acetic acid. The title compound is obtained as a light brown crystalline solid. Hexane), MS: m/e = 267 (M+H +). Example 399 (1 - ; r y y y y y y y y y y Ethyl-8-yl-1 oxime-imidazole-4-carboxylate was reacted with diisobutylhydrogenation. After hydrolysis and subsequent chromatography, the title compound was obtained as a light brown crystalline solid. C (Ethyl ether), MS: m/e = 225 (M+). Example 400 1H-Spider' Stupid two-gas Wuyuan-5-Kimijun-4-One 1A-Base 1 - 2 Stone is - Follow Example 301 of the schematic method '(1-Baohe [L3] Dioxin Garden _5_基_

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1328584

The 1H-imidazol-4-yl)-methanol was first treated with sulfinium gas and then treated with 2 - imidazole and cesium carbonate. The title compound was obtained as a light brown solid after evaporation, extraction, and chromatography. Melting point &gt; 156 ° C decomposition (dioxane / diisopropyl), MS: m / e = 3 14 (M + H +). Example 401. h(3-Difluoromethyl-4-fluoro-jam V4.4.5.5-tetramethyl-anthracene 1.3.21 dioxanthene title compound was obtained according to Example 342 as a colorless oil (54%) Yield: 4-bromo-2-difluorodecyl-1-fluoro-benzene and hydrazine (pinaconate) diboron were used as starting materials. MS: m/e = 272 (M+). - "3-(1,1-Difluoro-ethyl)-Moth 1-4.4.5.5-Tetramethyl-[1,3.21 Diazepine title compound was obtained according to Example 342 as a colorless oil (60 % yield), using 1-oxa-3-(1,1-difluoro-ethyl)-benzene and Dai (Pinalacate) as the starting material. MS: m/e=268 (M+) Example 403 2-Π-Gas-5-trifluoromethyl-Benzene V4.4.5.5-Tetramethyl--anthracene, 3,21 Diazepine m_ The title compound was obtained according to Example 342 as a colorless oil. (48% yield) using 3-bromo-5-fluoro benzotrifluoro and hydrazine (pinaconate) diboron as starting material. MS: m/e = 290 (M+) 〇 Example 404 7-Ρ - Π. Difluoro-ethyl V4-gas-芄 1-4,4,5,5-tetradecyl-Π.3.21 二氲杂圜-160- degree Applicable to China National Standard (CNS) A4 size (210X297 mm)

Binding

1328584 A7 __B7 V. INSTRUCTION DESCRIPTION (157) The title compound was obtained according to Example 342 as 'yellow oil (28% yield)' using 4-bromo-2-(1,1-difluoro-ethyl)-1-fluoro -Benzene and hydrazine (Pinaconate) diboron as starting materials. MS: m/e = 286.2 (M+). Example 405 4-Bromo-2-diindolemethyl-1-fluoro-stuppy 5-bromo-2-fluorobenzaldehyde (2 g, 9.85 mmol) was dissolved in dioxane (50 mL). The reaction mixture was placed under an argon atmosphere and cooled to 0 °C. Diethylaminosulfur trifluoride (2.04 ml '14.78 mmol) was added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. It was then quenched with saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted with di-methane. The combined organic phases were dehydrated with sodium sulfate and evaporated to remove solvent. The title compound (1.55 g, 70%) MS·· m/e=226.0 (M+H+) ° Example 406 I->Smelly-3-(1,1-di-ethylethyl). The title compound is based on Example 405 (Net diethylaminosulfur trifluoride) '''''''''''' The title compound of phenyl ethyl ketone is in accordance with the reference method MQ Zhang, A. Haemers, D. Vanden Berghe, SR Pattyn, W. Bollaert, Journal of Heterocyclic Chemistry, 1991, 28, 673-683, 2'-fluorophenyl The ketone was prepared as a starting material. The reaction gave a pale-yellow solid (yield: 85%). MS: m/e = 205 s (M+). • 161 · The paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297) PCT 1328584 A7 B7 V. INSTRUCTIONS (158) EXAMPLE 408. 4-Bromo-2-indole, 1-difluoroethyl)-1-fluoro-benzene The title compound is in accordance with the reference method (8. Ding &amp; 1^1^511丨, 7'· Agatsuma, M. Matsuda, T. Ohta, Τ. Nunozawa, Τ. Endo · S. Nozoe, Chemical and Pharmaceutical Bulletin, 1992, Ying j 3185-3188) Using 3-(1, 1-Difluoro-ethyl)·4-fluoro-phenylamine was prepared as a starting material. The reaction gave a dark red liquid (yield 46%). </ RTI> <RTIgt; 1H). Example 409 2-Cyclopropyl-1H-imidazole in a solution of ethyl cyclopropanecarboxylate imidate (3 2.9 g, 291 mmol) in decyl alcohol (40 mL) Methyl acetal (34.5 mL, 320 mmol) and the reaction mixture was stirred for 2 days. The reaction mixture was concentrated, concentrated hydrochloric acid and water were added and the mixture was concentrated again. The residue was dissolved in water and the pH was adjusted to 8 and concentrated mixture by sodium carbonate. The brown residue was suspended in ethanol and filtered. The filtrate was concentrated to give 30.6 g (yel. MS: m/e = 107.1 (M - Η). Example 410 Cyclopropane Carboxylidene Ethyl Ester Hydrochloride A steady stream of gaseous hydrogen gas was slowly passed through a solution of cyclopropanecarbonitrile (25 g, 373 mmol) in ethanol (17.2 mL). After 15 hours, the reaction mixture was cooled to 0 ° C and diethyl ether was added dropwise. The title compound was precipitated as a colourless crystalline material (32.9 g, 220 m. MS: m/e = l 12.2 (M - Η). •162. This paper scale applies to the Chinese National Standard (CNS) Α4 specification (210 X 297 mm)

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1328584 A7 B7 V. INSTRUCTIONS INSTRUCTIONS (159 EXAMPLES 411 VBrom-1-A-2·(2-Methyl-Mimi-1·华甲华Λ-1Η-Imidazole (5-Bromo-1-methyl-1Η) -Imidazolyl-2-yl)-methanol (1.0 g, 5.24 mmol) and tetrabromodecane (2.48 ' 7.33 mmol) dissolved in THF (1 mL·ml) and cooled to 0 ° C. Triphenylphosphine (1.98 g, 7.33 mmol) was added portionwise over a minute. The reaction mixture was stirred at EtOAc for 1 hour to give a white precipitate. In the second flask, sodium hydride (1.05 g, 26.18 mmol, 60%) Suspension in DMF (20 ml) and cooling to 〇 ° C. 2 -Methylimidazole (2.15 g, 26.2 mmol) was added portionwise. The reaction mixture was stirred at 60 ° C for 30 minutes and cooled to 〇 ° After the mixture was stirred for 2 hours at room temperature, the mixture was quenched with aqueous saturated sodium hydrogen carbonate (50 mL). The solvent was removed in vacuo <RTI ID=0.0> m/e = 255_0 (M+). Example 412 (5-bromo-1-methyl-1H-imidazol-2-yl-V-indole-imidazole-2-indole (3.15 g, 28 mmol). 81111仳61§;?.乂·Nguyen; Medicinal Chemistry Research 7, 2, 1997, 123-136) suspended in THF (75 ml) at -20 ° C and slowly with N-bromosuccinimide (4.9 g) The reaction mixture was slowly warmed to room temperature and quenched with saturated aqueous sodium hydrogen carbonate (50 mL). Washed with saturated aqueous sodium hydrogencarbonate solution, dried over sodium sulfate, filtered and evaporated in vacuo. The residue was purified by chromatography (yield eluted with ethyl acetate / hexane = 1:1 then dioxane / oxime Alcohol = 95:05 elution) Obtained -163- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) Binding

K- 1328584 A7 B7 V. INSTRUCTIONS (160) Ingot formulation (wet granulation) The title compound (2.11 g, 67%) was obtained as white solid. MS: m/e = 191_2 (M+).

Example A Item Ingredient mg/ingot 5 mg 25 mg 100 mg 500 mg 1. Formula 1 Compound 5 25 100 500 2. Lactose anhydrous DTG 125 105 30 150 3. Sta-Rx 1500 6 6 6 30 4. Microcrystalline cellulose 30 30 30 150 5. Magnesium stearate 1 1 1 1 Total 167 167 167 831 Manufacturing Procedure 1. Mix items 1, 2, 3 and 4 and granulate with pure water. 2. Dry the granules at 50 °C. 3. Allow the particles to pass through the appropriate grinding equipment. 4. Add item 5 and mix for three minutes; pressurize with a suitable press. Example B Capsule Formulation Item Ingredients mg/ingot 5 mg 25 mg 100 mg 500 mg 1. Formula 1 Compound 5 25 100 500 -164- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 A7 B7 V. INSTRUCTIONS (161) 2. Aqueous lactose 159 123 148 — 3. Corn house powder 25 35 40 70 4. Talc 10 15 10 25 5. Magnesium stearate 1 2 2 5 Total 200 200 300 600 Manufacturing Procedure 1. Mix items 1, 2 and 3 for 30 minutes with a suitable mixer. 2. Add 4 and 5 items and mix for 3 minutes. 3. Fill in the appropriate capsules. 4. Add item 5 and mix for three minutes; compress on a suitable press. • 165- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm)

Claims (1)

1328584 A8 Patent No. 091101137|^#^—., _ Chinese patent application scope 4 for Qin (n&lt;·^丨g application for patent garden 1. A compound of formula I Wherein A is a group, p is a bite-2-yl, p is a bit -3-yl or a brigade _ι_棊; R / R are each a hydrogen 'halogen atom' C1-7 fluorenyl, c3_6 cycloalkyl 'C2_7 dilute base' tri-gas methyl' · 〇·trifluoromethyl, _s_ difluoromethyl 'S-Cu alkyl, Cu alkoxy, _chf2 ' -C (Ci.7 alkyl) F2 ' -〇 CHF2, phenyl, phenyl, hydroxy-hydroxy or amine or co-formed with any carbon atom attached to it at any adjacent position -CH=CH-CH=CH-'-CH=CH-CH=N-,- (CH2)3· ' ·0-(:Η2_0- ' -〇-CF2-〇-,_CH2-0-CH2- or -ch2ch2-o-; r3 hydrogen, Ci-7 alkyl 'C3.6 cycloalkyl , phenyl, sC, _7 alkyl, amine 'Cu alkyl-amine, · NHCCCO-Cu alkyl or hydroxy-q. 7 alkyl; r4/r5 from or attached to hydrogen or cU7 alkyl The carbon atoms together form -(CH2)4-; r6/r6' are each hydrogen or Cl_7 alkyl; the paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1328584 8 8 8 8 A BCD Patent Application The heterocyclic aromatic group has the following structural formula: a) ε) R7 is hydrogen, -CH2OH or Cu alkyl; and its pharmaceutically acceptable acid addition salt. 2. If the compound of claim 1 of the patent scope has the following formula Wherein Kl/R: each is hydrogen, a halogen atom, a Cu alkyl group, a trifluoromethyl 'S-Ci.7 alkyl group 'Ci_7 alkoxy'-OCHF2, a phenyl group, a bowl base' Or the amine group or the carbon atom to which it is attached is formed as -(CH2)3-,-0- -2. This paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm). 8 8 8 8 ABCD h2-〇-, -CH2-〇-CH2- or -CH2CH2-0-; is chloro ' CK 7 alkyl 'phenyl, s_Cl 7 alkyl, amine, Ci-7 alkyl-amine, _NhC(〇)_Ci7 alkyl or hydroxyalkyl; each of which is hydrogen or a C7 alkyl group, or a carbon atom to which they are attached, is formed as -(CH2)4-; each is hydrogen or Cw alkyl, respectively; The aromatic group R3 R4/R5 R6/R6, written with the following structural formula: nr R7 . /&quot;N &gt; a) / b) R7 e) c) ?7 greedy g) R7 3. Nitrogen or Ci_7 alkyl; and its pharmaceutically acceptable acid addition salt. Such as the compound of claim 1 or 2, having the following formula La -3- 1328584 Wherein A and R1 to R7 are as defined in the patent scope; or a is a phenyl group and R to R7 are as defined in the second item of the patent application. 4. For the compound of claim 3, wherein a is a phenyl group, and r丨 and r2 are each a c&quot;yard base, _CHF2, _c (Ci 7 alkyl) F2, cf3 or a tooth atom, or a corresponding carbon The atoms together form _(CH2)3_, R3 is a Cm alkyl or amine group, and R4, {^ and ..., and r6' is hydrogen. 5. The compound of claim 4, which is 1H.imidazole, gas-3-methylphenyl)-lH-imidazol-4-yl]methyl]-2-ethyl-, 1H-imidazole, 1-[[ι_(4- gas-3-mercaptophenyl)-1Η-imidazol-4-yl;|mercapto]_ 2-ethyl-, 1H-imidazole, dihydro·1H_茚·5 ·)))H imidazolyl] fluorenyl]-2-methyl-, 1H-imidazole, fluorine_3_(trifluoromethyl)phenyl]·1Η•imidazole_4·yl]methyl]-2-methyl Base-, ^ 1-[1-(4-Ga-3-indolyl-phenyl)·1Η•imidazole_4_yl-methyl]·1Η•imidazole_2_yl-amine; 1Η-imidazole,-II Fluoroethyl)phenyl]_1Η•imidazole-4·yl]methyl]-2-indenyl·, Α 1Η-imidazole' 1-[[1-(3-difluoromethyl-4(phenyl)) Ιη-imidazole_4yl]methyl]-2-methyl- or Α 1Η-imidazole, l-tn-p-dj-difluoroethyl)·4_fluorophenyl]_1Ηimidazole-4_yl]methyl ]-2-Methyl-» 6. If the compound of claim 1 or 2 has the following formula -4-, the paper scale applies to the Chinese National Standard (CNS) Α4 specification (210X 297 mm) 1328584 A8 B8 C8 --------D8 VI. Application for patent scope Wherein Α and R1 to R6' are as defined in claim 1; or a is a phenyl group and R丨 to R6 are as defined in the second item of the patent application. 7. The compound of claim 3, wherein A is a phenyl group, Ri and R2 are a tooth atom, R3 is a Cu alkyl group or hydrogen, and R4, R5 and R6, R6 are hydrogen. 8. A compound according to claim 7 which is i-(3,4-di-phenyl)-3-(2-methyl-imidazolyl-methyl)-ex-pyrazole. 9. If the compound of claim 1 or 2 of the patent application has the following formula Loading Order Wherein A and R1 to R6' are as defined in claim 1; or VIII is benzoquinone and R1 to R6' are as defined in the second claim. 10. The compound of claim 9 wherein a is phenyl, R1 and R2 are halogen atoms, R3 is C丨7 alkyl or hydrogen and R4, R5 and R6, and R6' is hydrogen. 11. The compound of claim 10, which is 1-(3,4·di-phenyl)-4.imidazol-1-yl-methyl-1Η-pyrazole or 1-(3,4- Dioxo-phenyl)-4-(2-曱-5- This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1328584 Base-mito-1-yl-methyl)·1Η_pyrazole. 12. If the compound of claim 1 or 2 of the patent application has the following formula Its tA and Ri to R7 are defined as the patent (4) w; or a is a phenyl and R to R7 are defined as the second item of the patent application. 13. A compound of claim 12, wherein A is phenyl, and R2 is an atom, hydrogen, CF4Cl.7 alkyl, r, Ci-7 or nitrogen, and R4, R5 and R6, R6 , for hydrogen. 14. A compound of claim 13 which is a 1H-flavor. Sit '2-mercapto-i_[[4_[3_(trifluoromethyl)phenyl]_1Ηimidazole_2_yl]methyl]-, 1Η-imi. Sit ' ι_[[4_(4-fluoro_3·methylphenyl)_11^-flavor. _2_2-yl] fluorenyl-2-methyl-, 1Η-味唾' 1-[[4-(3,4-diphenyl)-indole-imidazol-2-yl]methyl-2- Methyl- or 1 Η·M., Sit, 4-(4-fluoro-3-indolyl)-2-(1Η-imidazol-1-yl-methyl)-. 15. If the compound of claim 1 or 2 of the patent application has the following formula -6 - the paper scale applies to the Chinese National Standard (CNS) Α 4 specification (210X 297 mm) 1328584 16. 17. Where A&amp;R1 to R7 are defined as item 1 of the scope of the patent; or A is phenyl and R to R7 are defined as item 2 of the scope of the patent application. A compound according to claim 15 wherein A is a phenyl group, R2 is a Cw group, a south atom or a CF3, r, a Ci-7 alkyl or a nitrogen, and R4, R5 and R6, and R6' are hydrogen. The compound of claim 16 is 3-(3,4-dimethyl-phenyl)·5-(2·methyl-flavor. Sodium succinylmethylpyridinium, 3-(4) -fluoro-3-methyl-phenyl)_5_(2_fluorenyl, succinylmethylbupyridin 3-(4-azaindolyl-phenyl)_5_(2_mercapto-Miso small base ·Methyl) _ 比 啶 3-(3-chloro-4-fluoro-phenyl) _5 _ (2. 曱-- 嗅 + 基 基 甲基 甲基 或 或 或 or 3 · (4 · 冬冬三 I Base-phenyl)_5_(2_曱基_咪〇 sit-small-methyl bite 0. For a compound of the scope of the patent application or item 2, having the following formula 'This paper scale applies to China National Standard (CNS) Α 4 specifications (210 X 297 public) &quot; ' ' -- 1328584 Wherein A and R1 to R6' are defined as f, but the patent range is the same; or a is phenyl and Ri to R6 are defined as item 2 of the scope of the patent application. 19. The compound of claim 18, wherein VIII is a phenyl group, r1a R2 is a halogen atom, R3 is a q-alkyl group, and feet 4, r5 and r6, r hydrogen. ''' 20. The compound of claim 19, which is 4-(3,4-oxa-phenyl)_2-(2-methylimidazolium-methyl)pyridine. 21·If the compound of claim 1 or 2 of the patent application has the following formula &gt;9 wherein A and Ri to R6' are as defined in the patent application range β; or a is a phenyl group and R to R6 are as defined in the second item of the patent application. 22. The compound of claim 21, wherein VIII is phenyl, ... and R is a halogen atom, R3 is C丨7 alkyl, and 4, r5 and r6, r6 hydrogen. &quot;&quot;&quot; 23. The compound of claim 22, which is 2-(3,4-dichlorophenyl)_4_(2-methylimidazolium q-ylindenyl)pyridine. 24. A pharmaceutical composition for treating an indication for a disease based on an NMDA receptor subtype-specific occlusive agent, comprising - or a plurality of compounds of formula I as claimed in claim 1 or 2 or pharmaceutical acceptableness thereof Salt and inertia • 8 - 1328584 A8 B8 C8 Carrier. 25. The pharmaceutical composition according to claim 24, wherein the disease is an acute neurodegenerative form caused by stroke and brain trauma, a chronic neurodegenerative form, a neurodegenerative disease caused by a bacterial or viral infection, and a sorrow and Chronic or acute pain. 26_A method of a compound of the formula I as defined in claim 1 of the patent scope, the method comprising Or R2 IV with a compound of the formula The reaction is carried out at room temperature and after evaporation of the solvent to obtain a compound of the formula -9. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 public) 1328584 6. Patent application scope 8 8 8 8 ABCD or Wherein A is phenyl or pyridin-2- or 3-yl, R1-!^ is as defined in the first paragraph of the patent application and hal is bromine or gas, or b) is cleaved from the compound of the formula to remove the N protecting group. It is dissolved in EtOH and treated with hydrochloric acid to obtain a compound of the formula -10- This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 8 8 8 8 ABCD VIII IX 1328584 Patent Application Scope Wherein A and R^-R6 are as defined in claim 1 and p is an N protecting group such as 2-(trimethylsulfanyl)-ethoxymethyl, or c) a compound of the formula or And a compound of the formula R^r H R5 -11 - This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 χ 297 mm) 1328584 8 8 8 8 ABCD Patent application process 4 hours under heating to 1 〇〇 ° C to obtain the following compound Le If R4 Ig Patent: where A is a phenyl or pyridinium-2- or 3-yl group and Ri_R6 is as defined in the first item of the scope and hal is chlorine or bromine. 27. The method of claim 26, further comprising the step of converting the compound to a pharmaceutically acceptable salt. Formula 1 -12- 1328584 A8 B8 C8 D8 VI. Application No. 28. The use of a compound as claimed in claim 1 or 2 for the preparation of a treatment-based NMD A receptor subtype-specific occlusion An agent for treating a disease of an indication. 29. The use of claim 28, wherein the disease is an acute neurodegenerative form caused by stroke and brain trauma, a chronic neurodegenerative form, a neurodegenerative disorder caused by a bacterial or viral infection, and depression and chronic or acute pain. This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm)