SK17122000A3 - Spôsob stereochemicky riadenej výroby izomericky čistých vysoko substituovaných azacyklických zlúčenín - Google Patents

Spôsob stereochemicky riadenej výroby izomericky čistých vysoko substituovaných azacyklických zlúčenín Download PDF

Info

Publication number: SK17122000A3
Authority: SK; Slovakia
Prior art keywords: formula; compounds; group; lower alkyl; substituted
Prior art date: 1998-05-13

Application number

SK1712-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Reggelin

Timo Heinrich

Bernd Junker

Jochen Antel

Ulf Preuschoff

Original Assignee

Solvay Pharmaceuticals Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-05-13

Filing date

1999-05-10

Publication date

2001-04-09

1999-05-10 Application filed by Solvay Pharmaceuticals Gmbh filed Critical Solvay Pharmaceuticals Gmbh

2001-04-09 Publication of SK17122000A3 publication Critical patent/SK17122000A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 52
238000004519 manufacturing process Methods 0.000 title claims abstract description 16
150000004030 azacyclic compounds Chemical class 0.000 title claims abstract description 15
150000001875 compounds Chemical class 0.000 claims description 214
125000000217 alkyl group Chemical group 0.000 claims description 71
238000006243 chemical reaction Methods 0.000 claims description 52
-1 hydroxy- Chemical class 0.000 claims description 49
229910052739 hydrogen Inorganic materials 0.000 claims description 46
239000001257 hydrogen Substances 0.000 claims description 45
125000006239 protecting group Chemical group 0.000 claims description 44
125000004432 carbon atom Chemical group C* 0.000 claims description 41
239000002904 solvent Substances 0.000 claims description 35
125000004122 cyclic group Chemical group 0.000 claims description 33
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 29
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
230000008569 process Effects 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 24
125000001188 haloalkyl group Chemical group 0.000 claims description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
239000003153 chemical reaction reagent Substances 0.000 claims description 20
229910052717 sulfur Inorganic materials 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
238000003776 cleavage reaction Methods 0.000 claims description 16
230000007017 scission Effects 0.000 claims description 16
125000003884 phenylalkyl group Chemical group 0.000 claims description 14
125000002947 alkylene group Chemical group 0.000 claims description 13
125000004438 haloalkoxy group Chemical group 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 12
239000011593 sulfur Substances 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
230000005595 deprotonation Effects 0.000 claims description 10
238000010537 deprotonation reaction Methods 0.000 claims description 10
125000004430 oxygen atom Chemical group O* 0.000 claims description 10
230000001681 protective effect Effects 0.000 claims description 10
230000015572 biosynthetic process Effects 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 8
229910052786 argon Inorganic materials 0.000 claims description 7
150000001721 carbon Chemical group 0.000 claims description 7
125000002950 monocyclic group Chemical class 0.000 claims description 7
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
WVVZEEAORNADKL-UHFFFAOYSA-N 3h-oxathiadiazole 2-oxide Chemical compound O=S1NN=CO1 WVVZEEAORNADKL-UHFFFAOYSA-N 0.000 claims description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
125000002524 organometallic group Chemical group 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
238000006894 reductive elimination reaction Methods 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 4
125000006297 carbonyl amino group Chemical class [H]N([*:2])C([*:1])=O 0.000 claims description 4
125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 4
230000017105 transposition Effects 0.000 claims description 4
229910052723 transition metal Inorganic materials 0.000 claims description 3
150000003624 transition metals Chemical class 0.000 claims description 3
230000004913 activation Effects 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
230000008030 elimination Effects 0.000 claims description 2
238000003379 elimination reaction Methods 0.000 claims description 2
239000012038 nucleophile Substances 0.000 claims description 2
239000012434 nucleophilic reagent Substances 0.000 claims description 2
125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
125000004093 cyano group Chemical group *C#N 0.000 claims 1
239000012351 deprotecting agent Substances 0.000 claims 1
XOMQMMJNWFJFBZ-UHFFFAOYSA-N imino-methyl-(4-methylphenyl)-oxo-$l^{6}-sulfane Chemical compound CC1=CC=C(S(C)(=N)=O)C=C1 XOMQMMJNWFJFBZ-UHFFFAOYSA-N 0.000 claims 1
238000005978 reductive desulfurization reaction Methods 0.000 claims 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims 1
239000013067 intermediate product Substances 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
239000000243 solution Substances 0.000 description 63
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
239000012074 organic phase Substances 0.000 description 29
230000002829 reductive effect Effects 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000002585 base Substances 0.000 description 23
239000000203 mixture Substances 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
239000008346 aqueous phase Substances 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
230000003287 optical effect Effects 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
238000003756 stirring Methods 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
150000001299 aldehydes Chemical class 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
AEBWATHAIVJLTA-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalene Chemical compound C1CCC2CCCC21 AEBWATHAIVJLTA-UHFFFAOYSA-N 0.000 description 6
239000005909 Kieselgur Substances 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
238000007363 ring formation reaction Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
125000004434 sulfur atom Chemical group 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
235000019270 ammonium chloride Nutrition 0.000 description 5
230000000269 nucleophilic effect Effects 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000007858 starting material Substances 0.000 description 5
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 5
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
229910052772 Samarium Inorganic materials 0.000 description 4
125000001931 aliphatic group Chemical group 0.000 description 4
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
239000012071 phase Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
150000003138 primary alcohols Chemical class 0.000 description 4
KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 4
238000000926 separation method Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 3
AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WBLQOEONNIZSFM-UHFFFAOYSA-N CS(=N)=O Chemical compound CS(=N)=O WBLQOEONNIZSFM-UHFFFAOYSA-N 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
238000006751 Mitsunobu reaction Methods 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
150000001342 alkaline earth metals Chemical class 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
150000001576 beta-amino acids Chemical class 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
IFMWVBVPVXRZHE-UHFFFAOYSA-M chlorotitanium(3+);propan-2-olate Chemical compound [Cl-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-] IFMWVBVPVXRZHE-UHFFFAOYSA-M 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000007717 exclusion Effects 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 3
238000010534 nucleophilic substitution reaction Methods 0.000 description 3
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 3
239000002798 polar solvent Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
125000005555 sulfoximide group Chemical group 0.000 description 3
RXBQNMWIQKOSCS-UHFFFAOYSA-N (7,7-dimethyl-4-bicyclo[3.1.1]hept-3-enyl)methanol Chemical compound C1C2C(C)(C)C1CC=C2CO RXBQNMWIQKOSCS-UHFFFAOYSA-N 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
DDEFUMHWGOVFIH-UHFFFAOYSA-N 2,3,3a,4,5,6-hexahydro-1H-cyclopenta[b]pyrrol-6a-ylmethyl-imino-(4-methylphenyl)-oxo-lambda6-sulfane Chemical compound CC1=CC=C(C=C1)S(=O)(=N)CC12NCCC2CCC1 DDEFUMHWGOVFIH-UHFFFAOYSA-N 0.000 description 2
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
XZFDKWMYCUEKSS-UHFFFAOYSA-N 6,6-Dimethylbicyclo[3.1.1]heptan-2-one Chemical compound C1C2C(C)(C)C1CCC2=O XZFDKWMYCUEKSS-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
VZFBQGDTDXXFAI-UHFFFAOYSA-N C=CS(=N)=O Chemical class C=CS(=N)=O VZFBQGDTDXXFAI-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000003513 alkali Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229930013930 alkaloid Natural products 0.000 description 2
125000005037 alkyl phenyl group Chemical group 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
238000011914 asymmetric synthesis Methods 0.000 description 2
150000001555 benzenes Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
125000001589 carboacyl group Chemical group 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000006260 foam Substances 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
IWIKSPCFZVZFIT-UHFFFAOYSA-M magnesium;but-1-ene;bromide Chemical compound [Mg+2].[Br-].C[CH-]C=C IWIKSPCFZVZFIT-UHFFFAOYSA-M 0.000 description 2
DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
150000004032 porphyrins Chemical group 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002243 precursor Substances 0.000 description 2
150000003235 pyrrolidines Chemical class 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
125000006413 ring segment Chemical group 0.000 description 2
238000012216 screening Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
229910052719 titanium Inorganic materials 0.000 description 2
239000010936 titanium Substances 0.000 description 2
238000004448 titration Methods 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
AVMHMVJVHYGDOO-IHWYPQMZSA-N (z)-1-bromobut-2-ene Chemical compound C\C=C/CBr AVMHMVJVHYGDOO-IHWYPQMZSA-N 0.000 description 1
POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical compound N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 1
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
YMIIHJBTQLZXBV-UHFFFAOYSA-N 2-[tert-butyl(dimethyl)silyl]oxypropanal Chemical compound O=CC(C)O[Si](C)(C)C(C)(C)C YMIIHJBTQLZXBV-UHFFFAOYSA-N 0.000 description 1
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
UCZTUROBDISEKY-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptane Chemical compound C1C2C(C)(C)C1CCC2 UCZTUROBDISEKY-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
238000006218 Arndt-Eistert homologation reaction Methods 0.000 description 1
125000006847 BOC protecting group Chemical group 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
DKSUYXRABYYUCN-UHFFFAOYSA-N C1(CCCC1)S(=O)=N Chemical compound C1(CCCC1)S(=O)=N DKSUYXRABYYUCN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
RXBQNMWIQKOSCS-RKDXNWHRSA-N Myrtenol Natural products C1[C@H]2C(C)(C)[C@@H]1CC=C2CO RXBQNMWIQKOSCS-RKDXNWHRSA-N 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
NXDQNQZSYLJNBX-UHFFFAOYSA-N N=S(=O)C1=CCCC1 Chemical compound N=S(=O)C1=CCCC1 NXDQNQZSYLJNBX-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
238000006859 Swern oxidation reaction Methods 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000004808 allyl alcohols Chemical class 0.000 description 1
150000001371 alpha-amino acids Chemical class 0.000 description 1
235000008206 alpha-amino acids Nutrition 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000010640 amide synthesis reaction Methods 0.000 description 1
PRKQVKDSMLBJBJ-UHFFFAOYSA-N ammonium carbonate Chemical class N.N.OC(O)=O PRKQVKDSMLBJBJ-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
238000007068 beta-elimination reaction Methods 0.000 description 1
238000009835 boiling Methods 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
230000008859 change Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
RAJISUUPOAJLEQ-UHFFFAOYSA-N chloromethanamine Chemical class NCCl RAJISUUPOAJLEQ-UHFFFAOYSA-N 0.000 description 1
150000003997 cyclic ketones Chemical class 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
238000006477 desulfuration reaction Methods 0.000 description 1
230000023556 desulfurization Effects 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical compound [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000010354 integration Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
229960004873 levomenthol Drugs 0.000 description 1
150000002642 lithium compounds Chemical class 0.000 description 1
GQNMAZUQZDEAFI-UHFFFAOYSA-N lithium;1h-naphthalen-1-ide Chemical compound [Li+].[C-]1=CC=CC2=CC=CC=C21 GQNMAZUQZDEAFI-UHFFFAOYSA-N 0.000 description 1
229940041616 menthol Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical class ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
230000006340 racemization Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011946 reduction process Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000005922 selenation reaction Methods 0.000 description 1
229940065287 selenium compound Drugs 0.000 description 1
150000003343 selenium compounds Chemical class 0.000 description 1
239000003579 shift reagent Substances 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
108010003641 statine renin inhibitory peptide Proteins 0.000 description 1
150000003459 sulfonic acid esters Chemical class 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
DCRJYOYBXFBHRD-CYDGBPFRSA-N tert-butyl (2s,3s,4s,5s)-4-hydroxy-2,3-dimethyl-5-(2-methylpropyl)pyrrolidine-1-carboxylate Chemical compound CC(C)C[C@H]1[C@@H](O)[C@@H](C)[C@H](C)N1C(=O)OC(C)(C)C DCRJYOYBXFBHRD-CYDGBPFRSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
XHJBJTVGPBSIEG-XNUZUHMRSA-N tert-butyl-dimethyl-[(2R)-3-methyl-2-[[methyl-(4-methylphenyl)-oxo-lambda6-sulfanylidene]amino]butoxy]silane Chemical compound [Si](C)(C)(C(C)(C)C)OC[C@@H](C(C)C)N=S(=O)(C1=CC=C(C=C1)C)C XHJBJTVGPBSIEG-XNUZUHMRSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229910052726 zirconium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D291/00—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms
- C07D291/02—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms not condensed with other rings
- C07D291/04—Five-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyrrole Compounds (AREA)
Indole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

SK1712-2000A 1998-05-13 1999-05-10 Spôsob stereochemicky riadenej výroby izomericky čistých vysoko substituovaných azacyklických zlúčenín SK17122000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19821418		1998-05-13
PCT/DE1999/001417 WO1999058500A1 (de)	1998-05-13	1999-05-10	Verfahren zur stereochemisch kontrollierten herstellung isomerenreiner hochsubstituierter azacyclischer verbindungen

Publications (1)

Publication Number	Publication Date
SK17122000A3 true SK17122000A3 (sk)	2001-04-09

Family

ID=7867628

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1712-2000A SK17122000A3 (sk)	1998-05-13	1999-05-10	Spôsob stereochemicky riadenej výroby izomericky čistých vysoko substituovaných azacyklických zlúčenín

Country Status (28)

Country	Link
US (1)	US6900322B1 (pt)
EP (1)	EP1076646B1 (pt)
JP (1)	JP4503833B2 (pt)
KR (1)	KR20010043475A (pt)
CN (1)	CN1252052C (pt)
AR (1)	AR016247A1 (pt)
AT (1)	ATE272621T1 (pt)
AU (1)	AU758192B2 (pt)
BR (1)	BR9911770A (pt)
CA (1)	CA2331758C (pt)
DE (2)	DE19921580A1 (pt)
DK (1)	DK1076646T3 (pt)
DZ (1)	DZ2787A1 (pt)
ES (1)	ES2228074T3 (pt)
HU (1)	HUP0101808A3 (pt)
ID (1)	ID26787A (pt)
IL (1)	IL139519A0 (pt)
NO (1)	NO317986B1 (pt)
NZ (1)	NZ508043A (pt)
PL (1)	PL197406B1 (pt)
PT (1)	PT1076646E (pt)
RU (1)	RU2225395C2 (pt)
SK (1)	SK17122000A3 (pt)
TR (1)	TR200003291T2 (pt)
TW (1)	TWI220143B (pt)
UA (1)	UA66859C2 (pt)
WO (1)	WO1999058500A1 (pt)
ZA (1)	ZA200006337B (pt)

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Publication number	Priority date	Publication date	Assignee	Title
US7119207B2 (en)	2000-04-10	2006-10-10	Pfizer Inc	Benzoamide piperidine containing compounds and related compounds
AP2002002647A0 (en) *	2000-04-10	2002-12-31	Pfizer Prod Inc	Benzoamide piperidine compounds as substance p antagonists
US7968734B2 (en) *	2004-07-01	2011-06-28	Stc.Unm	Organocatalysts and methods of use in chemical synthesis
CN103096893B (zh)	2010-06-04	2016-05-04	阿尔巴尼分子研究公司	甘氨酸转运体-1抑制剂、其制备方法及其用途

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5102877A (en) *	1989-04-28	1992-04-07	Fujisawa Pharmaceutical Co., Ltd.	1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds
US5100891A (en) *	1991-01-18	1992-03-31	Hoechst-Roussel Pharmaceuticals Inc.	Substituted 1,2,3,4-tetrahydrocyclopent[b]indoles, 1,2,3,3a,4,8a-hexahydrocyclopent[B]indoles and related compounds
TW214545B (pt)	1992-02-17	1993-10-11	Ciba Geigy Ag
US5252747A (en) *	1992-09-11	1993-10-12	Abbott Laboratories	Chiral quinolone intermediates

1999
- 1999-04-12 TW TW088105798A patent/TWI220143B/zh not_active IP Right Cessation
- 1999-04-30 AR ARP990102039A patent/AR016247A1/es not_active Application Discontinuation
- 1999-05-10 WO PCT/DE1999/001417 patent/WO1999058500A1/de not_active Ceased
- 1999-05-10 ID IDW20002335A patent/ID26787A/id unknown
- 1999-05-10 KR KR1020007012538A patent/KR20010043475A/ko not_active Ceased
- 1999-05-10 DE DE19921580A patent/DE19921580A1/de not_active Withdrawn
- 1999-05-10 JP JP2000548304A patent/JP4503833B2/ja not_active Expired - Fee Related
- 1999-05-10 NZ NZ508043A patent/NZ508043A/en unknown
- 1999-05-10 IL IL13951999A patent/IL139519A0/xx unknown
- 1999-05-10 HU HU0101808A patent/HUP0101808A3/hu unknown
- 1999-05-10 TR TR2000/03291T patent/TR200003291T2/xx unknown
- 1999-05-10 DK DK99934470T patent/DK1076646T3/da active
- 1999-05-10 UA UA2000127162A patent/UA66859C2/uk unknown
- 1999-05-10 CN CNB998057444A patent/CN1252052C/zh not_active Expired - Fee Related
- 1999-05-10 ES ES99934470T patent/ES2228074T3/es not_active Expired - Lifetime
- 1999-05-10 AT AT99934470T patent/ATE272621T1/de not_active IP Right Cessation
- 1999-05-10 RU RU2000131167/04A patent/RU2225395C2/ru not_active IP Right Cessation
- 1999-05-10 PL PL344043A patent/PL197406B1/pl not_active IP Right Cessation
- 1999-05-10 EP EP99934470A patent/EP1076646B1/de not_active Expired - Lifetime
- 1999-05-10 BR BR9911770-3A patent/BR9911770A/pt not_active IP Right Cessation
- 1999-05-10 AU AU50250/99A patent/AU758192B2/en not_active Ceased
- 1999-05-10 SK SK1712-2000A patent/SK17122000A3/sk unknown
- 1999-05-10 PT PT99934470T patent/PT1076646E/pt unknown
- 1999-05-10 CA CA002331758A patent/CA2331758C/en not_active Expired - Fee Related
- 1999-05-10 DE DE59910141T patent/DE59910141D1/de not_active Expired - Lifetime
- 1999-05-10 US US09/700,278 patent/US6900322B1/en not_active Expired - Fee Related
- 1999-05-12 DZ DZ990087A patent/DZ2787A1/xx active
2000
- 2000-11-06 ZA ZA200006337A patent/ZA200006337B/en unknown
- 2000-11-10 NO NO20005666A patent/NO317986B1/no unknown

Also Published As

Publication number	Publication date
CA2331758A1 (en)	1999-11-18
DK1076646T3 (da)	2004-09-06
ES2228074T3 (es)	2005-04-01
AU758192B2 (en)	2003-03-20
RU2225395C2 (ru)	2004-03-10
DE59910141D1 (de)	2004-09-09
HK1036624A1 (en)	2002-01-11
WO1999058500B1 (de)	1999-12-29
CN1252052C (zh)	2006-04-19
UA66859C2 (uk)	2004-06-15
EP1076646A1 (de)	2001-02-21
PL344043A1 (en)	2001-09-24
TR200003291T2 (tr)	2001-03-21
HUP0101808A2 (hu)	2001-09-28
IL139519A0 (en)	2001-11-25
NO20005666L (no)	2000-11-10
HUP0101808A3 (en)	2002-05-28
NZ508043A (en)	2003-05-30
TWI220143B (en)	2004-08-11
DE19921580A1 (de)	1999-11-25
EP1076646B1 (de)	2004-08-04
WO1999058500A1 (de)	1999-11-18
AR016247A1 (es)	2001-06-20
BR9911770A (pt)	2001-02-06
PL197406B1 (pl)	2008-03-31
CA2331758C (en)	2009-01-20
JP2002514624A (ja)	2002-05-21
JP4503833B2 (ja)	2010-07-14
AU5025099A (en)	1999-11-29
DZ2787A1 (fr)	2003-12-01
PT1076646E (pt)	2004-10-29
ATE272621T1 (de)	2004-08-15
US6900322B1 (en)	2005-05-31
ZA200006337B (en)	2001-05-16
NO317986B1 (no)	2005-01-17
CN1299345A (zh)	2001-06-13
NO20005666D0 (no)	2000-11-10
KR20010043475A (ko)	2001-05-25
ID26787A (id)	2001-02-08

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