CN118580237A - Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof - Google Patents
Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof Download PDFInfo
- Publication number
- CN118580237A CN118580237A CN202310192207.2A CN202310192207A CN118580237A CN 118580237 A CN118580237 A CN 118580237A CN 202310192207 A CN202310192207 A CN 202310192207A CN 118580237 A CN118580237 A CN 118580237A
- Authority
- CN
- China
- Prior art keywords
- pyrido
- compound
- hydrogen
- phenylpropenyl
- dmso
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Insects & Arthropods (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于化学合成技术领域，具体涉及含β‑苯丙烯基的吡啶并[1,2‑a]嘧啶酮衍生物及其制备方法和应用。本发明提供了一种含β‑苯丙烯基的吡啶并[1,2‑a]嘧啶酮衍生物，其对害虫表现出极高的灭杀活性，杀虫谱广，在制备杀虫剂方面具有广阔的应用前景；并且该含β‑苯丙烯基的吡啶并[1,2‑a]嘧啶酮衍生物的制备方法具有原料易得，反应条件温和，产率高等优点，非常适于大规模产业化生产。The present invention belongs to the technical field of chemical synthesis, and specifically relates to a pyrido [1,2-a] pyrimidone derivative containing a β-phenylpropenyl group, and a preparation method and application thereof. The present invention provides a pyrido [1,2-a] pyrimidone derivative containing a β-phenylpropenyl group, which exhibits extremely high killing activity against pests, has a wide insecticide spectrum, and has broad application prospects in the preparation of pesticides; and the preparation method of the pyrido [1,2-a] pyrimidone derivative containing a β-phenylpropenyl group has the advantages of easy availability of raw materials, mild reaction conditions, high yield, etc., and is very suitable for large-scale industrial production.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis. More particularly, it relates to a pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl, a preparation method and application thereof.
Background
New nicotine pesticides represented by imidacloprid are rapidly becoming an important component of the global pesticide market due to the advantages of high efficiency, broad spectrum, high selectivity and the like. However, with the extensive, long-term and unlimited use of neonicotinoid insecticides, pest resistance problems and bee toxicity problems are increasingly emerging (Han Minghui, fang Hong, wang Yuanping, wang He Xin, jiang Qing five. Neonicotinoid pesticide contamination and human exposure and adverse effects research [ J ]. Shanghai preventive medicine, 2021,33 (06 (: 534-543.DOI: 10.19428/j.cnki.sjpm.2021.20818.).
The plant essential oil can also be used as an insecticide, and has better effects than synthetic insecticides in terms of both environmental impact and human health. Cinnamon essential oil is taken as a fine-bodied ingredient in plant essential oil, and the active ingredient cinnamaldehyde in the cinnamon essential oil has been proved to have better insecticidal activity for many times. However, most of plant essential oils including cinnamon essential oils have slow action time and lower insecticidal activity than synthetic pesticides, so that large-scale popularization cannot be achieved.
Therefore, under the increasingly strict situation of pesticide use on environment, research on more efficient pesticide types with smaller dosage is of great significance.
Disclosure of Invention
The invention aims to overcome the defects and shortcomings of the existing common pesticides that pests have drug resistance, high toxicity, easy residue and slow action, and provides the pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl, which is efficient to the pests and small in dosage.
It is another object of the present invention to provide a process for the preparation of said beta-phenylpropenyl-containing pyrido [1,2-a ] pyrimidinone derivatives.
It is another object of the present invention to provide the use of said beta-phenylpropenyl containing pyrido [1,2-a ] pyrimidinone derivatives in pesticides.
It is another object of the present invention to provide an insecticide comprising said beta-phenylpropenyl pyrido [1,2-a ] pyrimidinone derivative.
The above object of the present invention is achieved by the following technical scheme:
A pyrido [1,2-a ] pyrimidinone derivative containing a β -phenylpropenyl group, having a molecular structure represented by formula (i (formula:
Wherein R 1 is selected from C 1～5 alkyl, phenyl, halophenyl, halogenated C 1～3 alkyl substituted phenyl, benzyl or halogenated C 1～3 alkyl substituted benzyl; r 2 is selected from hydrogen, halogen, or C 1～6 alkyl; r 3 is selected from hydrogen, halogen, halogenated C 1～6 alkyl or C 1～6 alkoxy; r 4 is selected from hydrogen or C 1～6 alkyl.
Preferably, wherein R 1 is selected from C 1～3 alkyl, phenyl, chlorophenyl, fluoromethane substituted phenyl, benzyl or fluoromethane substituted benzyl; r 2 is selected from hydrogen, halogen, or C 1～6 alkyl; r 3 is selected from hydrogen, halogen, fluoromethyl or C 1～3 alkoxy; r 4 is selected from hydrogen or C 1～3 alkyl.
More preferably, wherein R 1 is selected from methyl, phenyl, 3, 5-dichlorophenyl, 3- (trifluoromethyl) phenyl, benzyl or 3- (trifluoromethyl) benzyl; r 2 is selected from hydrogen, bromo, methyl, pentyl or hexyl; r 3 is selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl or methoxy; r 4 is selected from hydrogen or methyl.
More preferably, wherein R 1 is selected from 3, 5-dichlorophenyl, 3- (trifluoromethyl) phenyl, benzyl or 3- (trifluoromethyl) benzyl; r 2 is selected from hydrogen or bromine; r 3 is selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl or methoxy; r 4 is selected from hydrogen.
More preferably, R 1 is selected from benzyl, 3, 5-dichlorophenyl, 3- (trifluoromethyl) phenyl, or 3- (trifluoromethyl) benzyl; r 2 is selected from hydrogen; r 3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; r 4 is selected from hydrogen.
The invention also provides a preparation method of the pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl, which comprises the steps of dissolving an intermediate compound h and an intermediate compound c in toluene or xylene, reacting completely at 100-110 ℃, and carrying out post-treatment to obtain a target compound l:
Wherein R 1～R4 is as defined in any one of claims 1 to 4.
Preferably, the reaction is completed for 3 to 6 hours.
Preferably, the intermediate compound h: the molar mass ratio of the intermediate compound c is 1-3: 1.
Preferably, the post-treatment comprises the steps of: after the reaction, the target compound l is obtained by column chromatography gradient separation.
Further, intermediate compound h may be self-made or purchased.
Still further, when R 1 is selected from C 1～5 alkyl, phenyl, benzyl or halogenated C 1～3 alkyl substituted benzyl, the synthetic route for the intermediate compound h is as follows:
the method specifically comprises the following steps:
s1, adding sodium into absolute ethyl alcohol, completely dissolving, adding diethyl malonate, reacting for 1-2 h, adding a compound d, fully reacting at 70-80 ℃, and performing post-treatment to obtain a compound e;
s2, dissolving the compound e obtained in the step S1 in dichloromethane: methanol (V: v=1 to 12:1 (mixed solvent, fully reacted with sodium hydroxide at room temperature, post-treated) to give compound f;
s3, adding water into the compound f obtained in the step S2, dropwise adding an acidic reagent to adjust the pH to 2-3, fully reacting at room temperature, and performing post-treatment to obtain a compound g;
S4, adding 2,4, 6-trichlorophenol and phosphorus oxychloride into the compound g obtained in the step S3, fully reacting at 100-106 ℃, and carrying out post-treatment to obtain an intermediate compound h.
Preferably, in step S1, the time for the sufficient reaction is 1 to 2 hours.
Preferably, in step S1, the post-processing includes the steps of: after the reaction is finished, removing solid impurities by suction filtration, and spin-drying the reaction liquid to obtain the compound e.
Preferably, in step S1, the metal sodium: diethyl malonate: the molar mass ratio of the compound d is 1:1:1 to 1.5.
Preferably, in step S2, the time for the sufficient reaction is 3 to 5 hours.
Preferably, in step S2, the compound e: the molar mass ratio of the sodium hydroxide is 1:2 to 4.
Preferably, in step S2, the post-processing includes the steps of: after the reaction, the reaction mixture was dried by spin-drying to obtain compound f.
Preferably, in step S3, the acidic reagent is hydrochloric acid, nitric acid, sulfuric acid, or acetic acid.
More preferably, in step S3, the acidic reagent is hydrochloric acid.
Preferably, in step S3, the time for the sufficient reaction is 0.5 to 1h.
Preferably, in step S3, the post-processing includes the steps of: the residue was extracted with ethyl acetate, and the organic layer was dried over anhydrous MgSO 4 and concentrated to give compound g.
Preferably, in step S4, the time for the sufficient reaction is 3 to 4 hours.
Preferably, in step S4, the compound g: the molar mass ratio of the 2,4, 6-trichlorophenol is 1:1 to 2.
Preferably, in step S4, the post-processing includes the steps of: after the reaction is finished, the whole reaction system is poured into an ice-water mixture, a viscous substance is separated out after a period of time, the viscous substance is transferred into a round-bottom flask, absolute ethyl alcohol is added, stirring is carried out at room temperature, and suction filtration is carried out, thus obtaining an intermediate compound h.
Further, when R 1 is selected from the group consisting of halogenated phenyl and halogenated C 1～3 alkane substituted phenyl, the synthetic route of the intermediate compound h is as follows:
the method specifically comprises the following steps:
s1, dissolving R 5 substituted phenylacetic acid in toluene or xylene, adding a thionyl chloride catalyst, reacting for 3-4 hours at 100-110 ℃, adding methanol, fully reacting at 55-65 ℃, and carrying out post-treatment to obtain a compound d;
S2, sequentially adding dimethyl carbonate and tetrahydrofuran, slowly adding sodium hydride in batches, dropwise adding the compound d obtained in the step S1, fully reacting at 60-68 ℃, and performing post-treatment to obtain a compound e;
S3, dissolving the compound e obtained in the step S2 in absolute ethyl alcohol, fully reacting with sodium hydroxide at room temperature, and carrying out post-treatment to obtain a compound f;
s4, adding water into the compound obtained in the step S3, dropwise adding an acidic reagent to adjust the pH to 2-3, fully reacting at room temperature, and performing post-treatment to obtain a compound g;
S5, dissolving the compound g obtained in the step S4 in dichloromethane, adding dimethylformamide and oxalyl chloride, reacting for 1-2 hours at room temperature, adding 2,4, 6-trichlorophenol, reacting completely, and carrying out post-treatment to obtain an intermediate compound h;
Wherein R 5 is selected from halogen or halogenated C 1～3 alkyl, and R 1 is formed by R 5 and phenyl connected with the R 5.
Preferably, in step S1, the time for the sufficient reaction is 3 to 4 hours.
Preferably, in step S1, the post-processing includes the steps of: after the reaction, the reaction mixture was dried by spin-drying, extracted with ethyl acetate, and the organic layer was dried over anhydrous MgSO 4 or anhydrous Na 2SO4 and desolventized under reduced pressure to give compound d.
Preferably, in step S1, the R 5 replaces phenylacetic acid: the molar mass ratio of the thionyl chloride is 1:1 to 3.
Preferably, in step S2, the time for the sufficient reaction is 6h.
Preferably, in step S2, the compound d: the molar mass ratio of sodium hydride is 1:4.
Preferably, in step S2, the post-processing includes the steps of: after the reaction, the reaction mixture was dried, extracted with ethyl acetate, diethyl ether or dichloromethane, and the organic layer was dried over anhydrous MgSO 4 or anhydrous Na 2SO4 and desolventized under reduced pressure to give compound e.
Preferably, in step S3, the time for the sufficient reaction is 3 to 6 hours.
Preferably, in step S3, the compound e: the molar mass ratio of the sodium hydroxide is 1:1 to 2.
Preferably, in step S3, the post-processing includes the steps of: after the reaction, the compound f is obtained by decompression desolventizing.
Preferably, in step S4, the acidic reagent is hydrochloric acid, nitric acid, sulfuric acid, or acetic acid.
More preferably, in step S4, the acidic reagent is hydrochloric acid.
Preferably, in step S4, the time for the sufficient reaction is 0.5 to 1h.
Preferably, in step S4, the compound g: the molar mass ratio of the 2,4, 6-trichlorophenol is 1:1 to 2.
Preferably, in step S4, the post-processing includes the steps of: after the reaction was completed. Extraction with ethyl acetate, drying the organic layer over anhydrous MgSO 4 or anhydrous Na 2SO4, and concentration gave compound g.
Preferably, in step S5, the time for the sufficient reaction is 2h.
Preferably, in step S5, the compound g: the molar mass ratio of the 2,4, 6-trichlorophenol is 1:2.
Preferably, in step S5, the post-processing includes the steps of: after the reaction is finished, decompression desolventizing is carried out, ethanol is added into the residue for dissolution, the mixture is placed into a refrigerator for overnight precipitation of white solid, and the intermediate compound h is obtained through suction filtration.
Further, intermediate compound c may be self-made or purchased.
Further, the synthetic route of the intermediate compound c is as follows:
Further, when R 2 is selected from hydrogen, R 3 is selected from hydrogen, halogen, halogenated C 1～6 alkyl or C 1～6 alkoxy, the synthetic route of intermediate compound C specifically includes the following steps:
And (3) under the condition of protective gas atmosphere and room temperature, R 4 is substituted for 2-aminopyridine and the compound a, anhydrous sodium sulfate is added, acetic acid is dripped into the compound a, the compound b is obtained after reaction for 3 to 6 hours, absolute ethyl alcohol is added, sodium borohydride is slowly added in batches, the reaction is fully carried out, and the intermediate compound c is obtained after post treatment.
Preferably, the shielding gas includes helium, neon, argon and nitrogen.
More preferably, the shielding gas is argon.
Preferably, the time for the sufficient reaction is 4 hours.
Preferably, the post-treatment comprises the steps of: after the completion of the reaction, acetic acid was added to quench the reaction, the reaction mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous MgSO 4 or anhydrous Na 2SO4, concentrated, and the residue was separated by column chromatography to give compound c.
Preferably, the molar mass ratio of the R 4 substituted 2-aminopyridine to the compound a is 1:1 to 2.5.
Further, when R 2 is selected from halogen or C 1～6 alkyl, and R 3 is selected from hydrogen, the synthetic route of the intermediate compound C specifically includes the following steps:
Under the atmosphere of protective gas and the room temperature condition, R 4 substituted 2-aminopyridine is dissolved in absolute ethyl alcohol, ferric sulfate and a compound a are added for reaction for 2-6 hours at the temperature of 40-50 ℃ to obtain a compound b, sodium borohydride is slowly added in batches, the reaction is fully carried out under the room temperature condition, and the intermediate compound c is obtained after the post-treatment.
Preferably, the shielding gas includes helium, argon, neon, and nitrogen.
More preferably, the shielding gas is nitrogen.
Preferably, the time for the sufficient reaction is 4 hours.
Preferably, the post-treatment comprises the steps of: the reaction solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous MgSO 4 or anhydrous Na 2SO4, concentrated, and the residue was separated by column chromatography to give compound c.
Preferably, the R 4 substituted 2-aminopyridine: compound a: the molar mass ratio of the ferric sulfate is 1:1 to 1.5:0.4 to 0.5.
Furthermore, the invention also provides application of the pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl as an insecticide.
Preferably, the pests killed by the insecticide include aedes albopictus, german cockroach, and housefly.
Further, the invention also provides an insecticide comprising the pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl.
The invention has the following beneficial effects:
The pyrido [1,2-a ] pyrimidinone derivative containing beta-phenylpropenyl shows extremely high insecticidal activity on pests, has a broad insecticidal spectrum, and has a broad application prospect in the aspect of preparing pesticides; the preparation method of the pyrido [1,2-a ] pyrimidinone derivative containing the beta-phenylpropenyl has the advantages of easily available raw materials, mild reaction conditions, high yield and the like, and is very suitable for large-scale industrialized production.
Detailed Description
The present invention is further illustrated below with reference to specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Reagents and materials used in the following examples are commercially available unless otherwise specified.
Wherein, the synthetic route of the pyrido [1,2-a ] pyrimidinone derivative (namely the compound 1l-40 l) of the beta-phenylpropenyl is as follows:
example 1 Synthesis of intermediates 1c-11c
The synthetic route of the intermediate compounds 1c-11c is as follows:
the method specifically comprises the following steps:
s1, under the protection of argon, adding R 4 substituted 2-aminopyridine (1.88 g,20mmol,1eq (20 mL benzene, 3g anhydrous sodium sulfate) into a 100mL round bottom flask with a stirrer at room temperature, slowly dripping and dissolving 10mL cinnamaldehyde (compound a) substituted by different benzene rings (25 mmol,1.25eq (5 drops acetic acid) at room temperature, stirring for 6h at room temperature, filtering after the reaction is finished, spinning the filtrate to obtain a compound b, immediately adding the compound b into the next reaction without purification, adding 30mL absolute ethyl alcohol into the 100mL round bottom flask, fully dissolving, weighing 2.9g sodium borohydride, adding the sodium borohydride in batches, stirring for 4h at room temperature, adding 1mL acetic acid for quenching reaction, spinning the reaction liquid, separating residues by column chromatography, and eluting with petroleum ether ethyl acetate=8:1 (v/v (% to obtain an intermediate 1c-7 c).
S2, under the protection of nitrogen, taking absolute ethyl alcohol as a solvent at room temperature, adding R 4 to replace 2-aminopyridine and ferric sulfate, dripping different alpha-substituted cinnamaldehyde (compound a), reacting at 50 ℃ for 3 hours to obtain a compound b, after the reaction is finished, slowly adding sodium borohydride in batches, reacting at room temperature for 4 hours, and after the reaction is finished, adding acetic acid to quench. The reaction solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous MgSO 4, concentrated, and the residue was separated by column chromatography to give intermediate 8c-11c.
EXAMPLE 2 Synthesis of target Compound ll-26l
The synthetic route of the target compounds 1l-26l is as follows:
S1, cutting sodium block (0.46 g,20mmol,1eq (and cutting off surface oxide layer, adding into 50mL flask, adding 30mL absolute ethanol immediately, stirring at room temperature until sodium block completely disappears, adding diethyl malonate (3.2 g,20mmol,1eq (stirring at room temperature for 1h, then weighing compound d (25 mmol (adding into reaction system, heating system to 80deg.C for 2h, TLC plate tracking reaction progress (petroleum ether: ethyl acetate=8:1 (after reaction end, removing solid impurities by suction, spin-drying reaction solution) to obtain compound e).
S2. compound e (20 mmol,1eq (charged into a 250mL round bottom flask and added with dichloromethane: methanol (V: v=9:1) solvent 100mL, sodium hydroxide (3.2 g,80mmol,4eq (, stirred for 5h at room temperature, tlc plate followed the progress of the reaction (petroleum ether: ethyl acetate=8:1 (. After the end of the reaction, the reaction was dried by spin) to give compound f).
S3 to compound f (15 mmol,1 eq) (50 mL of water, 1M hydrochloric acid slowly added dropwise to adjust pH to 2. 150mL of water, ethyl acetate (50 mL. Times.3, liquid-phase extraction, washing 3 times with 100mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying the solvent) was added to the residue to give compound g.
Into a round bottom flask of S4.100mL was added compound g (15 mmol,1eq (, 2,4, 6-trichlorophenol (5.9 g,30mmol,2eq (, phosphorus oxychloride 30mL,106 ℃ C.) under stirring and refluxing for 4h. After completion of the reaction, the whole reaction system was poured into 300mL of ice-water mixture and a viscous substance was precipitated after a while, the viscous substance was transferred to a round bottom flask of 100mL, 60mL of absolute ethanol was added, stirring was performed at room temperature for 1h, and suction filtration was performed to obtain intermediate h.
S5, weighing an intermediate h (5 mmol,1 eq) (intermediate c (5 mmol,1eq (30 mL toluene is taken as a reaction solvent in a 100mL three-port bottle, the temperature is firstly increased to 80 ℃ for half an hour, then the temperature is increased to 90 ℃, the temperature is increased to 110 ℃ every half an hour after the temperature is increased to 10 ℃ for each half an hour, the reaction is finished for 6 hours, and after the reaction is finished, the column chromatography gradient separation is carried out, and the eluent is petroleum ether, namely ethyl acetate=1:1 (v/v (, ethyl acetate, methanol=15:1 (v/v (, so as to obtain a target product of 1l-26 l).
EXAMPLE 3 Synthesis of target Compound 27l-40l
The synthesis route of the target compounds 27l-40l is as follows:
| 27l:R5＝3-CF3,R2＝H,R3＝4-Cl,R4＝H | 34l:R5＝3,5-Cl,R2＝H,R3＝H,R4＝H |
| 28l:R5＝3-CF3,R2＝H,R3＝4-Br,R4＝H | 35l:R5＝3,5-Cl,R2＝H,R3＝4-Cl,R4＝H |
| 29l:R5＝3-CF3,R2＝H,R3＝4-F,R4＝H | 36l:R5＝3,5-Cl,R2＝H,R3＝4-Br,R4＝H |
| 30l:R5＝3-CF3,R2＝H,R3＝3-CF3,R4＝H | 37l:R5＝3,5-Cl,R2＝H,R3＝4-F,R4＝H |
| 31l:R5＝3-CF3,R2＝H,R3＝4-OCH3,R4＝H | 38l:R5＝3,5-Cl,R2＝H,R3＝3-CF3,R4＝H |
| 32l:R5＝3-CF3,R2＝Br,R3＝H,R4＝H | 39l:R5＝3,5-Cl,R2＝H,R3＝4-OCH3,R4＝H |
| 33l:R5＝3-CF3,R2＝H,R3＝H,R4＝CH3 | 40l:R5＝3,5-Cl,R2＝H,R3＝H,R4＝CH3 |
s1: r 5 substituted phenylacetic acid (25 mmol,1 eq), thionyl chloride (75 mmol,3eq (, 20mL toluene was added to a 100mL round bottom flask, reflux was performed at 110 ℃ for 4h, the reaction mixture was dried by spin-drying after the completion of the reaction), the obtained acid chloride was slowly dropped into a round bottom flask containing 50mL methanol, reflux was performed at 65 ℃ for 3h, the reaction mixture was dried by spin-drying after the completion of the reaction, 100mL water and ethyl acetate (50 mL. Times.3) were added to extract in a liquid-separated manner, the organic phase was washed 3 times with 100mL saturated sodium chloride solution, dried over anhydrous magnesium sulfate, desolventized under reduced pressure, and the residue was separated by column chromatography (petroleum ether: ethyl acetate=10:1 (, to give compound d).
S2: 20mL of dimethyl carbonate and 20mL of tetrahydrofuran are taken and added into a 250mL round bottom flask, sodium hydride (7.2 g,30mmol,1.5 eq) is slowly added in batches (compound d (20 mmol,1 eq) is slowly added dropwise after the addition is finished, reflux reaction is carried out for 6h at 68 ℃, a TLC (thin layer chromatography) point plate tracks the reaction progress (petroleum ether: ethyl acetate=5:1), the reaction solution is dried after the reaction is finished, 150mL of water and (50 mL multiplied by 3) of ethyl acetate are added into the reaction residue for liquid extraction, an organic phase is washed 3 times with 100mL of saturated sodium chloride solution, anhydrous magnesium sulfate is dried, and the compound e is obtained after decompression and desolventization.
S3: to a 100mL round bottom flask was added compound e (15 mmol,1 eq), 50mL absolute ethanol, stirred slowly at room temperature for 10min, after it was completely dissolved sodium hydroxide (2.3 g,60mmol,3 eq) was added, stirred at room temperature for 6h, tlc plate followed the progress of the reaction (petroleum ether: ethyl acetate=10:1 (.
S4: to compound f (15 mmol,1 eq) was added 50mL of water, and 1M hydrochloric acid was slowly added dropwise under ice bath to adjust pH to 2-3, and the mixture was reacted at room temperature for 1h. 150mL of water was added thereto, ethyl acetate (50 mL. Times.3) was extracted by liquid-separating, and the organic phase was washed 3 times with 100mL of a saturated sodium chloride solution, dried over anhydrous sodium sulfate and desolventized under reduced pressure to obtain compound g.
S5: to a 100mL round bottom flask equipped with a stirrer was added compound g (10 mmol,1eq (25 mL of dichloromethane, 1mL of DMF, 2mL of oxalyl chloride were slowly added dropwise thereto, and after stirring at room temperature for 2 hours, 2,4, 6-trichlorophenol (3.94 g,20mmol,2eq (, stirring at room temperature was continued for 2 hours, after completion of the reaction, desolventizing under reduced pressure), 100mL of ethanol was added to the residue, and a white solid was precipitated in a refrigerator overnight, and the intermediate compound h was obtained by suction filtration.
S6: the intermediate compound h (5 mmol,1 eq) is weighed, the intermediate compound c (5 mmol,1 eq) is put into a 100mL three-port bottle, 30mL toluene is taken as a reaction solvent, the temperature is firstly increased to 80 ℃, the temperature is increased to 90 ℃ after half an hour, the temperature is increased to 10 ℃ every half an hour until the temperature reaches 110 ℃, the reaction is carried out for 6 hours, and after the reaction is finished, the column chromatography gradient separation is carried out, the eluent is petroleum ether, namely ethyl acetate=1:1 (v/v (, ethyl acetate, methanol=15:1 (v/v), and 27l-40l of target products are obtained.
The mass spectrum data and molecular structural formula of the obtained 40 target compounds 1l-40l are as follows:
1-cinnamyl-3-methyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (1 l):
Yellow soild,(yield:37.2％(,mp:124-125℃1 1H NMR(600MHz,DMSO-d6(δ9.24(dd,J＝6.9,1.6Hz,1H(,8.23(ddd,J＝8.8,7.0,1.7Hz,1H(,7.78(dt,J＝9.0,0.9Hz,1H(,7.51–7.43(m,1H(,7.43–7.36(m,2H(,7.29(t,J＝7.7Hz,2H(,7.24–7.19(m,1H(,6.57–6.51(m,1H(,6.35(dt,J＝16.1,5.2Hz,1H(,5.33–4.78(m,2H(,1.94(s,3H(.13C NMR(151MHz,DMSO(δ159.44,154.09,145.92,142.80,136.56,131.73,131.04,129.00,128.14,126.76,124.13,116.37,114.84,88.34,44.00,11.03.HRMS(ESI(:Extract mass calculated for C18H16N2O2[M+H]+:293.12911Found:293.1299.
(E) -1- (3- (4-chlorophenyl) allyl) -3-methyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (2 l):
Yellow soild,(yield:31.2％(,mp:111-112℃1 1H NMR(600MHz,DMSO-d6(δ9.24(ddd,J＝6.8,1.7,0.6Hz,1H(,8.23(ddd,J＝8.8,7.0,1.7Hz,1H(,7.90–7.67(m,1H(,7.47(td,J＝6.9,1.1Hz,1H(,7.44–7.39(m,2H(,7.37–7.29(m,2H(,6.56–6.46(m,1H(,6.39(dt,J＝16.2,5.1Hz,1H(,5.17–4.93(m,2H(,1.94(s,3H(.13CNMR(151MHz,DMSO(δ159.43,154.10,145.93,142.83,135.57,132.49,131.03,130.27,128.97,128.49,125.24,116.40,114.84,88.34,43.94,11.02.HRMS(ESI(:Extract mass calculated for C18H15ClN2O2[M+2H]+:328.08221Found:328.0822
(E) -1- (3- (4-bromophenyl) allyl) -3-methyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (3 l):
Yellow soild,(yield:37.4％(,mp:136-137℃1 1H NMR(600MHz,DMSO-d6(δ9.23(dd,J＝6.9,1.6Hz,1H(,8.22(ddd,J＝8.9,7.0,1.7Hz,1H(,7.76(dt,J＝9.0,0.9Hz,1H(,7.50–7.44(m,3H(,7.38–7.32(m,2H(,6.53–6.45(m,1H(,6.40(dt,J＝16.2,5.0Hz,1H(,5.21–4.84(m,2H(,1.94(s,3H(.13C NMR(151MHz,DMSO(δ159.43,154.11,145.92,142.83,135.92,131.88,131.03,130.32,129.70,129.21,128.81,125.33,121.06,116.40,114.84,88.35,43.95,11.02.Extract mass calculated for C18H15BrF3N2O2[M+H]+:371.03961Found:371.0381.
1-cinnamyl-4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (4 l):
Yellow soild,(yield:60.6％(,mp:146-147℃1 1H NMR(600MHz,DMSO-d6(δ9.32(ddd,J＝6.9,1.7,0.6Hz,1H(,8.29(ddd,J＝8.9,7.0,1.7Hz,1H(,7.83(dt,J＝9.1,1.0Hz,1H(,7.78–7.62(m,2H(,7.50(td,J＝6.9,1.1Hz,1H(,7.44–7.37(m,2H(,7.34–7.27(m,4H(,7.27–7.19(m,1H(,7.19–7.13(m,1H(,6.66–6.57(m,1H(,6.39(dt,J＝16.1,5.3Hz,1H(,5.12(d,J＝5.3Hz,2H(.13C NMR(151MHz,DMSO(δ158.67,153.78,146.52,143.69,136.60,135.96,131.94,131.50,131.23,129.01,128.17,127.35,126.78,125.69,124.08,116.59,114.96,94.00,44.22.HRMS(ESI(:Extract mass calculated for C23H18N2O2[M+H]+:355.14471Found:355.1442.
(E) -1- (3- (4-chlorophenyl) allyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (5 l):
Yellow soild,(yield:60.3％(,mp:134-135℃1 1H NMR(600MHz,DMSO-d6(δ9.32(dd,J＝6.9,1.6Hz,1H(,8.28(ddd,J＝8.9,7.0,1.7Hz,1H(,7.89–7.75(m,1H(,7.75–7.67(m,2H(,7.50(td,J＝7.0,1.1Hz,1H(,7.46–7.40(m,2H(,7.37–7.27(m,4H(,7.18–7.11(m,1H(,6.63–6.53(m,1H(,6.49–6.38(m,1H(,5.11(d,J＝5.1Hz,2H(.13C NMR(151MHz,DMSO(δ158.66,153.79,148.07,146.53,143.71,137.38,135.94,135.61,132.52,131.50,131.22,130.48,128.99,128.51,127.35,125.69,125.19,116.62,114.97,112.25,108.43,93.99,44.15.HRMS(ESI(:Extract mass calculated for C23H17ClN2O2[M+H]+:389.11371Found:389.1161.
(E) -1- (3- (4-bromophenyl) allyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (6 l):
Yellow soild,(yield:48.9％(,mp:154-155℃1 1H NMR(600MHz,DMSO-d6(δ9.32(dd,J＝6.9,1.6Hz,1H(,8.28(ddd,J＝8.9,7.0,1.7Hz,1H(,7.80(d,J＝9.0Hz,1H(,7.73–7.66(m,2H(,7.53–7.45(m,3H(,7.40–7.34(m,2H(,7.30(t,J＝7.8Hz,2H(,7.16(tt,J＝7.2,1.3Hz,1H(,6.64–6.55(m,1H(,6.53–6.38(m,1H(,5.10(d,J＝5.1Hz,2H(.13C NMR(151MHz,DMSO(δ158.65,153.79,146.54,143.71,135.97,135.95,132.58,131.90,131.50,131.22,130.52,129.75,128.83,127.99,127.34,125.69,125.30,122.98,121.08,116.62,114.99,93.97,44.16.HRMS(ESI(:Extract mass calculated for C23H17BrF3N2O3[M+H]+:433.05521Found:433.0557.
(E) -1- (3- (4-fluorophenyl) allyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (7 l):
Yellow soild,(yield:56.7％(,mp:156-157℃1 1H NMR(600MHz,DMSO-d6(δ9.32(ddd,J＝6.9,1.7,0.6Hz,1H(,8.29(ddd,J＝8.9,7.0,1.7Hz,1H(,7.81(dt,J＝9.1,1.0Hz,1H(,7.76–7.67(m,2H(,7.55–7.42(m,3H(,7.41–7.22(m,2H(,7.19–7.05(m,3H(,6.69–6.51(m,1H(,6.35(dt,J＝16.0,5.2Hz,1H(,5.10(d,J＝5.2Hz,2H(.13C NMR(151MHz,DMSO(δ162.93,161.31,157.46,155.28,153.78,146.53,143.69,135.97,131.49,131.22,130.68,128.74,128.69,127.34,125.68,124.01,124.00,116.60,115.90,115.76,114.98,93.98,44.16.HRMS(ESI(:Extract mass calculated for C23H17FN2O2[M+H]+:373.13531Found:373.1379.
(E) -4-oxo-3-phenyl-1- (3- (3- (trifluoromethyl) phenyl) allyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (8 l):
Yellow soild,(yield:57.1％(,mp:188-189℃1 1H NMR(600MHz,DMSO-d6(δ9.33(dd,J＝6.9,1.6Hz,1H(,8.29(ddd,J＝8.8,7.0,1.7Hz,1H(,7.89–7.61(m,6H(,7.62–7.42(m,3H(,7.31(t,J＝7.7Hz,2H(,7.22–7.07(m,1H(,6.79–6.46(m,1H(,5.23–5.04(m,2H(.13C NMR(151MHz,DMSO(δ158.65,153.82,146.58,143.71,137.87,135.98,131.47,131.23,130.42,130.05,129.87,127.34,126.67,125.67,124.45,124.42,123.43,123.41,123.12,116.62,115.05,93.99,44.11,40.58.HRMS(ESI(:Extract mass calculated for C24H17F3N2O2[M+H]+:423.13211Found:423.1316.
(E) -1- (3- (4-methoxyphenyl) allyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (9 l):
Yellow soild,(yield:55.4％(,mp:177-178℃1 1H NMR(600MHz,DMSO-d6(δ9.31(dd,J＝6.9,1.6Hz,1H(,8.29(ddd,J＝8.8,7.0,1.7Hz,1H(,7.83(d,J＝9.0Hz,1H(,7.78–7.63(m,2H(,7.50(td,J＝6.9,1.0Hz,1H(,7.37–7.27(m,4H(,7.26–7.08(m,1H(,6.97–6.76(m,2H(,6.58(dd,J＝16.2,1.6Hz,1H(,6.22(dt,J＝16.1,5.4Hz,1H(,5.08(d,J＝5.4Hz,2H(,3.73(s,3H(.13C NMR(151MHz,DMSO(δ159.42,158.67,153.76,146.49,143.65,135.98,131.73,131.48,131.23,129.23,128.08,127.34,125.68,121.43,116.56,114.97,114.44,94.01,55.57,44.28.HRMS(ESI(:Extract mass calculated for C24H20N2O3[M+H]+:385.15531Found:385.1546.
(E) -1- (2-methyl-3-phenylallyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (10 l):
Yellow soild,(yield:37.6％(,mp:124-125℃1 1H NMR(600MHz,DMSO-d6(δ9.33(dd,J＝6.9,1.6Hz,1H(,8.30(ddd,J＝8.8,6.9,1.7Hz,1H(,7.79–7.63(m,3H(,7.52(t,J＝7.0Hz,1H(,7.31(td,J＝7.7,3.9Hz,4H(,7.25–7.14(m,4H(,6.26(s,1H(,5.03(s,2H(,1.90(s,3H(.13C NMR(151MHz,DMSO(δ158.84,153.78,146.75,143.71,137.19,135.99,132.57,131.53,131.25,129.70,129.23,128.58,128.21,127.34,126.99,125.69,124.75,116.72,115.11,99.99,93.84,48.88,16.13.HRMS(ESI(:Extract mass calculated for C24H20N2O2[M+H]+:369.16041Found:369.1629.
(E) -1- (2-benzylidene ethyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (11 l):
Yellow soild,(yield:38.5％(,mp:156-157℃1 1H NMR(600MHz,DMSO-d6(δ9.33(ddd,J＝6.8,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,7.76–7.58(m,3H(,7.52(td,J＝6.9,1.1Hz,1H(,7.35–7.27(m,4H(,7.23–7.12(m,4H(,6.21(s,1H(,5.07(s,2H(,2.35–2.16(m,2H(,1.56(q,J＝7.5,7.1Hz,2H(,1.31–1.22(m,4H(,0.90–0.75(m,3H(.13C NMR(151MHz,DMSO(δ158.78,153.74,146.74,143.70,137.15,136.69,135.99,131.57,131.25,128.87,128.67,127.35,127.08,125.71,124.98,116.71,115.11,93.88,47.45,31.85,29.55,27.75,22.18,14.29.HRMS(ESI(:Extract mass calculated for C28H28N2O2[M+H]+:425.22301Found:425.2226.
(E) -1- (2-benzylidene-ethyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (12 l):
Yellow soild,(yield:41.2％(,mp:121-122℃1 1H NMR(600MHz,DMSO-d6(δ9.33(dd,J＝6.9,1.7Hz,1H(,8.30(ddd,J＝8.9,7.0,1.7Hz,1H(,7.86–7.60(m,3H(,7.60–7.45(m,1H(,7.35–7.25(m,4H(,7.23–7.12(m,4H(,6.22(s,1H(,5.06(s,2H(,2.50(p,J＝1.8Hz,1H(,2.32–2.17(m,2H(,1.54(ddd,J＝12.2,10.1,6.4Hz,2H(,1.33–1.15(m,7H(.13C NMR(151MHz,DMSO(δ158.78,153.73,146.74,143.70,137.15,136.71,135.99,133.34,132.11,131.99,131.57,131.25,131.21,128.87,128.67,127.34,127.08,125.71,125.07,116.71,115.11,93.87,47.46,31.31,29.52,29.27,28.03,22.45,14.35.HRMS(ESI(:Extract mass calculated for C29H30N2O2[M+H]+:439.23861Found:439.2363.
(Z) -1- (2-bromo-3-phenylallyl) -4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (13 l):
Yellow soild,(yield:42.3％(,mp:132-133℃1 1H NMR(600MHz,DMSO-d6(δ9.35(ddd,J＝14.3,6.8,1.6Hz,1H(,8.40(dddd,J＝55.3,8.8,7.0,1.7Hz,1H(,7.79(d,J＝9.0Hz,1H(,7.69(ddt,J＝20.6,6.3,1.4Hz,2H(,7.62–7.52(m,2H(,7.47–7.26(m,6H(,7.24–7.11(m,2H(,5.41(d,J＝32.5Hz,2H(.13C NMR(151MHz,DMSO(δ157.90,157.39,153.15,146.05,145.47,143.57,135.24,134.58,131.49,131.20,130.61,128.69,128.52,128.03,126.78,125.15,118.84,116.62,114.30,93.10,83.48,49.52,32.24.HRMS(ESI(:Extract mass calculated for C23H17BrN2O2[M+H]+:433.05521Found:433.0558.
1-cinnamyl-9-methyl-4-oxo-3-phenyl-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (14 l):
Yellow soild,(yield:37.4％(,mp:171-172℃1 1H NMR(600MHz,DMSO-d6(δ9.33(s,J＝6.9,1.7Hz,1H(,7.77–7.63(m,3H(,7.52(t,J＝7.0Hz,1H(,7.31(td,J＝7.7,3.9Hz,4H(,7.25–7.14(m,4H(,6.55(s,1H(,6.25(s,1H(,5.33(s,2H(,1.95(s,3H(.13C NMR(151MHz,DMSO(δ157.87,154.54,146.77,144.00,137.76,137.20,134.68,131.07,130.43,130.06,128.89,129.91,128.89,128.29,126.50,124.45,124.24,122.99,116.86,115.25,92.22,44.41,33.21.Extract mass calculated for C24H20N2O2[M+H]+:369.16041Found:369.1635.
3-benzyl-1-cinnamyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (15 l):
Yellow soild,(yield:49.2％(,mp:176-177℃1 1H NMR(600MHz,DMSO-d6(δ9.25(ddd,J＝6.9,1.7,0.6Hz,1H(,8.24(ddd,J＝8.9,7.0,1.7Hz,1H(,7.79(dt,J＝9.0,1.0Hz,1H(,7.48(td,J＝6.9,1.1Hz,1H(,7.42–7.35(m,2H(,7.35–7.31(m,2H(,7.29(dd,J＝8.4,6.9Hz,2H(,7.25–7.16(m,3H(,7.13–7.06(m,1H(,6.55(dt,J＝16.1,1.7Hz,1H(,6.35(dt,J＝16.1,5.2Hz,1H(,5.22–4.92(m,2H(,3.79(s,2H(.13C NMR(151MHz,DMSO(δ159.39,154.31,146.31,143.17,142.56,136.53,134.03,131.88,131.31,128.99,128.85,128.25,128.15,127.63,127.11,126.76,126.18,125.74,124.94,124.10,116.49,114.93,93.07,44.09,30.98.HRMS(ESI(:Extract mass calculated for C24H20N2O2[M+H]+:369.16041Found:369.1649.
(E) -3-benzyl-1- (3- (4-chlorophenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (16 l):
Yellow soild,(yield:50.7％(,mp:138-139℃1 1H NMR(600MHz,DMSO-d6(δ9.24(ddd,J＝6.8,1.7,0.6Hz,1H(,8.23(ddd,J＝8.9,7.0,1.7Hz,1H(,7.76(dt,J＝9.1,1.0Hz,1H(,7.47(td,J＝6.9,1.1Hz,1H(,7.43–7.37(m,2H(,7.37–7.28(m,4H(,7.23–7.14(m,2H(,7.14–7.05(m,1H(,6.53(dt,J＝16.1,1.7Hz,1H(,6.38(dt,J＝16.2,5.2Hz,1H(,5.10–4.98(m,2H(,3.79(s,2H(.13C NMR(151MHz,DMSO(δ159.37,154.33,146.33,143.20,142.53,135.53,132.52,131.21,130.43,128.97,128.84,128.48,128.35,128.25,127.94,127.76,127.49,125.74,125.20,116.52,114.94,93.05,44.03,30.96.HRMS(ESI(:Extract mass calculated for C24H19ClN2O2[M+H]+:403.12141Found:403,1210.
(E) -3-benzyl-1- (3- (4-bromophenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (17 l):
Yellow soild,(yield:46.4％(,mp:145-146℃1 1H NMR(600MHz,DMSO-d6(δ9.25(ddd,J＝6.8,1.7,0.6Hz,1H(,8.24(ddd,J＝8.8,7.0,1.7Hz,1H(,7.77(dt,J＝9.1,1.0Hz,1H(,7.51–7.44(m,3H(,7.37–7.30(m,4H(,7.21–7.16(m,2H(,7.11–7.06(m,1H(,6.55–6.47(m,1H(,6.40(dt,J＝16.1,5.1Hz,1H(,5.17–4.93(m,2H(,3.78(s,2H(.13C NMR(151MHz,DMSO(δ159.37,154.33,146.35,143.20,142.54,135.90,131.89,131.21,130.47,129.52,128.84,128.81,128.25,125.74,125.32,121.08,116.52,114.96,93.02,44.03,31.40,30.97,22.51,14.40.HRMS(ESI(:Extract mass calculated for C24H19BrN2O2[M+H]+:447.07091Found:447.0706.
(E) -3-benzyl-1- (3- (4-fluorophenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (18 l):
Yellow soild,(yield:49.5％(,mp:150-151℃1 1H NMR(600MHz,DMSO-d6(δ9.24(ddd,J＝6.9,1.7,0.6Hz,1H(,8.24(ddd,J＝8.9,7.0,1.7Hz,1H(,7.77(dt,J＝9.1,1.0Hz,1H(,7.53–7.38(m,3H(,7.38–7.25(m,2H(,7.25–7.16(m,2H(,7.16–7.06(m,3H(,6.54(dt,J＝16.1,1.7Hz,1H(,6.39–6.21(m,1H(,5.12–4.97(m,2H(,3.78(s,2H(.13C NMR(151MHz,DMSO(δ162.93,161.31,158.65,146.53,143.69,135.97,133.23,133.21,131.49,131.23,130.67,128.74,128.69,127.34,125.68,124.01,123.99,116.60,115.91,115.76,114.99,93.98,44.16,41.16.HRMS(ESI(:Extract mass calculated for C24H19FN2O2[M+H]+:387.15101Found:387.1508.
(E) -3-benzyl-4-oxo-1- (3- (3- (trifluoromethyl) phenyl) allyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (19 l):
Yellow soild,(yield:49.2％(,mp:179-180℃1 1H NMR(600MHz,DMSO-d6(δ9.24(ddd,J＝6.8,1.7,0.6Hz,1H(,8.24(ddd,J＝8.8,7.0,1.7Hz,1H(,7.77(dt,J＝9.1,1.0Hz,1H(,7.53–7.37(m,3H(,7.37–7.28(m,2H(,7.28–7.16(m,2H(,7.16–7.03(m,3H(,6.54(dt,J＝16.2,1.7Hz,1H(,6.30(dt,J＝16.2,5.2Hz,1H(,5.17–5.00(m,2H(,3.78(s,2H(.13C NMR(151MHz,DMSO(δ162.36,160.74,158.82,153.76,145.76,142.62,141.97,132.58,130.63,130.07,128.27,128.17,128.11,127.69,127.14,125.18,123.45,123.43,115.94,115.33,115.19,114.39,92.49,43.47,30.39.HRMS(ESI(:Extract mass calculated for C25H19F3N2O2[M+H]+:437.14781Found:437.1466.
(E) -3-benzyl-1- (3- (4-methoxyphenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (20 l):
Yellow soild,(yield:50.6％(,mp:168-169℃1 1H NMR(600MHz,DMSO-d6(δ9.54–8.94(m,1H(,8.23(ddd,J＝8.9,7.0,1.7Hz,1H(,7.78(dt,J＝9.1,0.9Hz,1H(,7.46(td,J＝6.9,1.1Hz,1H(,7.32(td,J＝7.5,6.9,1.7Hz,4H(,7.19(t,J＝7.7Hz,2H(,7.09(td,J＝7.2,1.3Hz,1H(,6.87–6.72(m,2H(,6.50(d,J＝1.6Hz,1H(,6.17(d,J＝16.1Hz,1H(,5.11–4.96(m,2H(,3.75(d,J＝41.7Hz,5H(.13C NMR(151MHz,DMSO(δ159.42,159.40,154.30,146.29,143.14,142.56,131.67,131.19,129.17,128.84,128.25,128.07,125.74,121.45,116.46,114.94,114.43,93.09,55.56,44.15,30.97.HRMS(ESI(:Extract mass calculated for C25H22N2O3[M+H]+:399.17091Found:399.1725.
(E) -3-benzyl-1- (2-methyl-3-phenylallyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (21 l):
Yellow soild,(yield:34.2％(,mp:123-124℃1 1H NMR(600MHz,DMSO-d6(δ9.25(ddd,J＝6.8,1.7,0.6Hz,1H(,8.25(ddd,J＝8.9,7.0,1.7Hz,1H(,7.69(dt,J＝9.0,0.9Hz,1H(,7.49(td,J＝7.0,1.1Hz,1H(,7.35–7.27(m,4H(,7.19(td,J＝7.7,1.9Hz,5H(,7.11–7.06(m,1H(,6.16(d,J＝2.0Hz,1H(,5.00(s,2H(,3.80(s,2H(,1.87(d,J＝1.3Hz,3H(.13C NMR(151MHz,DMSO(δ159.58,154.29,146.52,143.21,142.57,137.10,132.64,131.25,129.17,128.76,128.59,128.25,126.99,125.74,124.69,116.63,115.06,92.91,48.74,30.97,16.09.HRMS(ESI(:Extract mass calculated for C25H22N2O2[M+H]+:383.17601Found:383.1773.
(E) -3-benzyl-1- (2-benzylideoethyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (22 l):
Yellow soild,(yield:30.7％(,mp:146-147℃1 1H NMR(600MHz,DMSO-d6(δ9.26(dd,J＝6.9,1.6Hz,1H(,8.27(ddd,J＝8.8,6.9,1.7Hz,1H(,7.64(d,J＝9.0Hz,1H(,7.49(t,J＝6.9Hz,1H(,7.37–7.26(m,4H(,7.26–7.03(m,6H(,6.16(s,1H(,5.05(s,2H(,3.80(s,2H(,2.27–2.12(m,2H(,1.51(dd,J＝9.8,5.6Hz,2H(,1.23(d,J＝4.1Hz,4H(,0.82(q,J＝3.7,2.9Hz,3H(.13C NMR(151MHz,DMSO(δ159.52,154.24,146.51,143.21,142.57,137.06,136.87,131.29,128.81,128.75,128.68,128.22,127.10,126.65,125.73,125.23,124.66,116.62,115.06,112.03,92.94,47.36,31.84,30.98,29.43,27.76,22.15,14.27.HRMS(ESI(:Extract mass calculated for C29H30N2O2[M+H]+:439.23861Found:439.2366.
(E) -3-benzyl-1- (2-benzylideoethyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (23 l):
Yellow soild,(yield:30.2％(,mp:118-119℃1 1H NMR(600MHz,DMSO-d6(δ9.25(dd,J＝6.9,1.6Hz,1H(,8.27(ddd,J＝8.9,7.0,1.7Hz,1H(,7.64(dd,J＝9.0,1.1Hz,1H(,7.49(td,J＝7.0,1.1Hz,1H(,7.34–7.28(m,4H(,7.22–7.16(m,3H(,7.14(dd,J＝7.8,1.2Hz,2H(,7.11–7.07(m,1H(,6.16(s,1H(,5.05(s,2H(,3.80(s,2H(,2.35–2.01(m,2H(,1.68–1.42(m,2H(,1.35–1.02(m,7H(,0.82(t,J＝7.0Hz,3H(.13C NMR(151MHz,DMSO(δ159.52,154.23,146.50,143.21,142.57,137.07,136.87,131.28,128.81,128.75,128.67,128.22,127.10,125.74,125.24,116.62,115.06,92.94,47.36,31.28,30.97,29.44,29.25,28.02,22.43,14.34.HRMS(ESI(:Extract mass calculated for C30H32N2O2[M+H]+:453.25431Found:453.2549.
(Z) -3-benzyl-1- (2-bromo-3-phenylallyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (24 l):
Yellow soild,(yield:40.2％(,mp:136-137℃1 1H NMR(600MHz,DMSO-d6(δ9.29(ddd,J＝6.8,1.7,0.6Hz,1H(,8.31(ddd,J＝8.9,7.1,1.7Hz,1H(,7.77(dt,J＝9.0,0.9Hz,1H(,7.63–7.45(m,3H(,7.45–7.26(m,5H(,7.19(t,J＝7.6Hz,2H(,7.12(s,2H(,5.38(d,J＝25.5Hz,2H(,3.80(s,2H(.13C NMR(151MHz,DMSO(δ159.21,154.26,146.46,143.67,142.44,135.11,131.52,130.05,129.82,129.54,129.26,128.79,128.69,128.63,128.26,128.12,128.01,125.76,119.51,117.06,114.87,92.67,49.94,30.96.HRMS(ESI(:Extract mass calculated for C24H19BrN2O2[M+H]+:447.07091Found:447.0737.
3-benzyl-1-cinnamyl-9-methyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (25 l):
Yellow soild,(yield:27.2％(,mp:165-166℃1 1H NMR(600MHz,DMSO-d6(δ9.26(ddd,J＝6.8,1.7,0.6Hz,1H(,7.69(dt,J＝9.0,0.9Hz,1H(,7.49(td,J＝7.0,1.1Hz,1H(,7.35–7.27(m,4H(,7.19(td,J＝7.7,1.9Hz,5H(,7.11–7.06(m,1H(,6.40(d,J＝2.0Hz,1H(,6.10(d,J＝2.0Hz,1H(,5.10(s,2H(,3.73(s,2H(,1.77(d,J＝1.3Hz,3H(.13C NMR(151MHz,DMSO(δ159.88,154.26,146.52,143.21,142.57,137.20,132.64,131.25,129.19,129.06,128.86,128.84,128.82,128.42,128.25,127.62,126.99,125.54,124.99,116.53,115.16,92.61,49.04,31.07,16.39.Extract mass calculated for C25H22N2O2[M+H]+:383.16811Found:383.1698.
1-cinnamyl-4-oxo-3- (3- (trifluoromethyl) benzyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (26 l):
Yellow soild,(yield:58.7％(,mp:169-170℃1 1H NMR(600MHz,DMSO-d6(δ9.34(ddd,J＝6.9,1.7,0.6Hz,1H(,8.32(ddd,J＝8.9,7.0,1.7Hz,1H(,8.19(m,1H(,8.15–8.09(m,1H(,7.85(dt,J＝9.1,0.9Hz,1H(,7.59–7.46(m,3H(,7.44–7.38(m,2H(,7.33–7.26(m,2H(,7.26–7.19(m,1H(,6.74–6.53(m,1H(,6.40(dt,J＝16.1,5.2Hz,1H(,5.23–5.03(m,2H(.13C NMR(151MHz,DMSO(δ158.70,154.00,146.68,144.16,137.20,136.61,134.70,131.95,131.60,129.01,128.39,128.29,128.18,127.17,126.79,126.04,124.24,123.93,122.01,116.82,115.13,99.99,92.63,44.33.HRMS(ESI(:Extract mass calculated for C25H19F3N2O2[M-CH]+:423.13211Found:423.1338.
(E) -1- (3- (4-chlorophenyl) allyl) -4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (27 l):
Yellow soild,(yield:46.8％(,mp:161-162℃1 1H NMR(600MHz,DMSO-d6(δ9.34(ddd,J＝6.9,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,8.18(dd,J＝2.3,1.3Hz,1H(,8.12(dq,J＝7.7,1.0Hz,1H(,7.83(dt,J＝9.0,0.9Hz,1H(,7.58–7.51(m,2H(,7.52–7.47(m,1H(,7.46–7.41(m,2H(,7.38–7.33(m,2H(,6.65–6.59(m,1H(,6.47–6.40(m,1H(.13C NMR(151MHz,DMSO(δ158.67,154.01,146.68,144.19,137.18,135.61,134.69,132.52,131.59,130.46,128.99,128.51,128.38,128.30,128.17,127.16,126.04,125.03,124.24,122.01,116.84,115.14,92.62,44.26.HRMS(ESI(:Extract mass calculated for C24H16ClF3N2O2[M+H]+:457.08671Found:457.0899.
(E) -1- (3- (4-bromophenyl) allyl) -4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (28 l):
Yellow soild,(yield:54.6％(,mp:166-167℃1 1H NMR(600MHz,DMSO-d6(δ9.34(ddd,J＝6.8,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,8.18(q,J＝1.8,1.4Hz,1H(,8.12(dt,J＝7.9,1.4Hz,1H(,7.83(dt,J＝9.0,0.9Hz,1H(,7.59–7.45(m,5H(,7.41–7.33(m,2H(,6.60(dt,J＝16.1,1.7Hz,1H(,6.45(dt,J＝16.2,5.1Hz,1H(,5.18–5.01(m,2H(.13C NMR(151MHz,DMSO(δ158.67,154.01,146.68,144.18,137.17,135.96,134.69,131.90,131.60,130.53,128.83,128.38,128.30,128.18,127.13,126.04,125.13,124.23,121.99,121.10,116.84,115.13,92.62,44.27.Extract mass calculated for C24H16BrF3N2O2[M+H]+:501.04261Found:501.0420.
(E) -1- (3- (4-fluorophenyl) allyl) -4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (29 l):
Yellow soild,(yield:47.5％(,mp:154-155℃1 1H NMR(600MHz,DMSO-d6(δ9.34(ddd,J＝6.9,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,8.18(h,J＝0.9Hz,1H(,8.12(dt,J＝7.9,1.2Hz,1H(,7.84(dt,J＝9.0,0.9Hz,1H(,7.59–7.36(m,5H(,7.19–7.05(m,2H(,6.63(dt,J＝16.2,1.7Hz,1H(,6.35(dt,J＝16.2,5.2Hz,1H(,5.11(d,J＝5.8Hz,2H(.13C NMR(151MHz,DMSO(δ161.31,158.68,154.00,146.68,144.17,137.19,134.69,133.23,131.59,130.69,128.75,128.70,128.29,127.16,127.13,123.84,123.83,122.00,116.83,115.91,115.77,115.14,92.62,44.27.HRMS(ESI(:Extract mass calculated for C24H16F4N2O2[M+H]+:441.12271Found:441.1222.
(E) -4-oxo-3- (3- (trifluoromethyl) phenyl) -1- (3- (3- (trifluoromethyl) phenyl) allyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (30 l):
Yellow soild,(yield:43.5％(,mp:149-150℃1 1H NMR(600MHz,DMSO-d6(δ9.34(ddd,J＝6.9,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,8.29–8.07(m,2H(,7.83(dt,J＝9.0,0.9Hz,1H(,7.58–7.46(m,3H(,7.45–7.39(m,2H(,7.37–7.33(m,2H(,6.69–6.24(m,2H(,5.12(d,J＝5.1Hz,2H(.13C NMR(151MHz,DMSO(δ158.67,154.04,146.72,144.20,137.86,137.20,134.68,131.57,130.42,130.06,129.89,129.81,128.39,128.29,126.50,126.04,124.44,124.24,123.44,123.41,121.99,116.86,115.20,92.62,44.21.HRMS(ESI(:Extract mass calculated for C25H16F6N2O2[M+H]+:491.11951Found:491.1174.
(E) -1- (3- (4-methoxyphenyl) allyl) -4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (31 l):
Yellow soild,(yield:49.4％(,mp:180-181℃1 1H NMR(600MHz,DMSO-d6(δ9.33(ddd,J＝6.9,1.7,0.6Hz,1H(,8.32(ddd,J＝8.8,7.0,1.7Hz,1H(,8.18(ddt,J＝1.9,1.3,0.7Hz,1H(,8.15–8.08(m,1H(,7.86(dt,J＝9.1,1.0Hz,1H(,7.59–7.45(m,3H(,7.38–7.29(m,2H(,6.91–6.81(m,2H(,6.64–6.53(m,1H(,6.22(dt,J＝16.1,5.5Hz,1H(,5.10(d,J＝5.4Hz,2H(,3.73(s,3H(.13C NMR(151MHz,DMSO(δ159.44,158.70,158.70,157.57,153.98,146.66,144.13,137.20,134.70,131.75,131.59,129.24,128.29,128.10,127.65,127.17,127.14,122.00,121.28,116.79,115.13,114.45,92.64,55.57,44.39.HRMS(ESI(:Extract mass calculated for C25H19F3N2O3[M+H]+:453.14271Found:453.1425.
(Z) -1- (2-bromo-3-phenylallyl) -4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (32 l):
Yellow soild,(yield:27.3％(,mp:169-170℃1 1H NMR(600MHz,DMSO-d6(δ9.38(ddd,J＝6.8,1.7,0.6Hz,1H(,8.39(ddd,J＝8.9,7.0,1.7Hz,1H(,8.18(d,J＝1.8Hz,1H(,8.13(dd,J＝7.9,1.4Hz,1H(,7.81(dt,J＝9.0,0.8Hz,1H(,7.63–7.48(m,5H(,7.40–7.29(m,3H(,7.20(s,1H(,5.42(d,J＝37.0Hz,2H(.13C NMR(151MHz,DMSO(δ158.52,153.97,146.77,144.67,137.06,135.16,134.68,131.90,129.29,129.12,128.69,128.63,128.61,128.42,128.35,128.34,128.21,127.11,122.09,119.19,117.40,115.04,92.36,50.22.HRMS(ESI(:Extract mass calculated for C24H16BrF3N2O3[M+H]+:501.04261Found:501.0394.
1-cinnamyl-9-methyl-4-oxo-3- (3- (trifluoromethyl) phenyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (33 l):
Yellow soild,(yield:35.4％(,mp:172-173℃1 1H NMR(600MHz,DMSO-d6(δ9.33(dd,J＝6.9,1.6Hz,1H(,7.77–7.63(m,3H(,7.52(t,J＝7.0Hz,1H(,7.31(td,J＝7.7,3.9Hz,3H(,7.25–7.14(m,4H(,6.52(s,1H(,6.25(s,1H(,5.33(s,2H(,1.91(s,3H(.13C NMR(151MHz,DMSO(δ157.84,153.88,146.76,143.73,137.19,135.99,135.99,135.44,132.57,132.01,131.53,131.25,130.10,129.79,129.28,128.58,128.49,127.32,126.99,125.59,124.75,116.52,115.16,93.83,47.88,16.33.HRMS(ESI(:Extract mass calculated for C25H19F3N2O2[M+H]+:437.14781Found:437.1499.
1-cinnamyl-3- (3, 5-dichlorophenyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (34 l):
Yellow soild,(yield:40.2％(,mp:165-166℃1 1H NMR(600MHz,DMSO-d6(δ9.32(dd,J＝6.9,0.6Hz,1H(,8.29(ddd,J＝8.9,7.0,1.7Hz,1H(,7.83(dt,J＝9.1,1.0Hz,1H(,7.78–7.62(m,1H(,7.44–7.37(m,2H(,7.34–7.27(m,4H(,7.19–7.13(m,2H(,6.66–6.57(m,1H(,6.39(dt,J＝16.1,5.3Hz,1H(,5.12(d,J＝5.3Hz,2H(.13C NMR(151MHz,DMSO(δ157.67,154.78,146.52,143.69,136.60,135.66,133.36,132.90,131.94,131.50,131.23,130.49,129.95,129.01,128.17,127.35,126.28,125.29,124.08,116.59,114.96,94.00,44.02.HRMS(ESI(:Extract mass calculated for C23H16Cl2N2O2[M+H]+:423.06691Found:423.0673.
(E) -1- (3- (4-chlorophenyl) allyl) -3- (3, 5-dichlorophenyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (35 l):
Yellow soild,(yield:51.3％(,mp:164-165℃1 1H NMR(600MHz,DMSO-d6(δ9.22(dd,J＝6.9,1.6Hz,1H(,8.18(ddd,J＝8.7,7.0,1.7Hz,1H(,7.89–7.75(m,1H(,7.74–7.67(m,2H(,7.50(td,J＝7.0,1.1Hz,1H(,7.37–7.27(m,4H(,7.17–7.11(m,1H(,6.63–6.53(m,1H(,6.49–6.38(m,1H(,5.11(d,J＝5.1Hz,2H(.13CNMR(151MHz,DMSO(δ158.86,153.99,148.37,146.53,142.73,137.38,135.94,135.84,135.64,132.62,131.53,131.22,130.48,128.89,128.50,127.35,125.72,125.19,116.62,114.92,112.25,93.93,44.66.HRMS(ESI(:Extract mass calculated for C23H15Cl3N2O2[M+H]+:457.02781Found:457.0267.
(E) -1- (3- (4-bromophenyl) allyl) -3- (3, 5-dichlorophenyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (36 l).
Yellow soild,(yield:48.9％(,mp:184-185℃1 1H NMR(600MHz,DMSO-d6(δ9.32(dd,J＝6.9,1.6Hz,1H(,8.28(ddd,J＝8.9,7.0,1.7Hz,1H(,7.80(d,J＝9.0Hz,1H(,7.73–7.66(m,2H(,7.53–7.45(m,2H(,7.40–7.34(m,2H(,7.30(t,J＝7.8Hz,1H(,7.16(tt,J＝7.2,1.3Hz,1H(,6.64–6.55(m,1H(,6.53–6.38(m,1H(,5.10(d,J＝5.1Hz,2H(.13C NMR(151MHz,DMSO(δ158.65,153.79,146.54,143.71,135.97,135.95,133.10,131.90,131.50,131.22,130.52,129.75,128.83,127.34,125.69,125.30,124.61,121.08,118.26,116.62,114.99,93.97,44.76.HRMS(ESI(:Extract mass calculated for C23H15Br2Cl2N2O2[M+H]+:500.97731Found:500.9765.
(E) -3- (3, 5-dichlorophenyl) -1- (3- (4-fluorophenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (37 l):
Yellow soild,(yield:46.7％(,mp:186-187℃1 1H NMR(600MHz,DMSO-d6(δ9.32(ddd,J＝6.9,1.7,0.6Hz,1H(,8.29(ddd,J＝8.9,7.0,1.7Hz,1H(,7.81(dt,J＝9.1,1.0Hz,1H(,7.76–7.67(m,2H(,7.55(dt,J＝15.7,5.2Hz,1H(,7.41–7.22(m,2H(,7.19–7.05(m,3H(,6.69–6.51(m,1H(,6.35(dt,J＝16.0,5.2Hz,1H(,5.10(d,J＝5.2Hz,2H(.13C NMR(151MHz,DMSO(δ158.67,154.01,146.68,144.19,137.18,135.61,134.69,133.25,132.52,131.59,130.46,129.78,128.99,128.51,128.30,127.16,126.04,125.03,122.01,116.84,115.14,92.62,44.26.HRMS(ESI(:Extract mass calculated for C23H15FCl2N2O2[M+H]+:441.05711Found:441.0566.
(E) -3- (3, 5-dichlorophenyl) -4-oxo-1- (3- (3- (trifluoromethyl) phenyl) allyl) -4H-pyrido [1,2-a ] pyrimidin-1-ium-2-ol (38 l):
Yellow soild,(yield:41.1％(,mp:188-189℃1 1H NMR(600MHz,DMSO-d6(δ9.34(dd,J＝6.9,1.6Hz,1H(,8.29(ddd,J＝8.8,7.0,1.7Hz,1H(,7.89–7.61(m,4H(,7.60–7.42(m,3H(,7.31(t,J＝7.7Hz,1H(,7.22–7.07(m,1H(,6.69–6.67(m,1H(,6.61–6.59(m,1H(,5.21–5.09(m,2H(.13C NMR(151MHz,DMSO(δ158.85,153.85,146.58,143.31,137.87,135.94,131.47,131.43,130.42,130.05,129.88,127.24,126.77,125.67,124.46,123.72,123.43,123.34,116.22,115.99,115.55,93.99,43.91.HRMS(ESI(:Extract mass calculated for C24H15Cl2F3N2O2[M+H]+:491.05421Found:491.0562.
(E) -3- (3, 5-dichlorophenyl) -1- (3- (4-methoxyphenyl) allyl) -4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (39 l):
Yellow soild,(yield:35.4％(,mp:187-188℃1 1H NMR(600MHz,DMSO-d6(δ9.31(dd,J＝6.9,1.6Hz,1H(,8.29(ddd,J＝8.8,7.0,1.7Hz,1H(,7.83(d,J＝9.0Hz,1H(,7.76–7.61(m,2H(,7.50(td,J＝6.9,1.0Hz,1H(,7.37–7.29(m,4H(,7.26–7.08(m,1H(,6.97–6.76(m,2H(,6.58(dd,J＝16.2,1.6Hz,1H(,6.22(dt,J＝16.1,5.4Hz,1H(,5.08(d,J＝5.4Hz,2H(,3.73(s,3H(.13C NMR(151MHz,DMSO(δ159.42,158.67,153.76,146.49,143.65,135.98,134.12,131.73,131.48,131.23,129.23,128.08,127.34,125.68,124.03,121.43,118.69,116.56,114.97,114.44,112.90,94.01,55.57,44.28.HRMS(ESI(:Extract mass calculated for C24H18Cl2N2O3[M+H]+:453.07731Found:453.0769.
1-cinnamyl-3- (3, 5-dichlorophenyl) -9-methyl-4-oxo-4H-pyrido [1,2-a ] pyrimidin-1-onium-2-ol (40 l):
Yellow soild,(yield:34.4％(,mp:171-172℃1 1H NMR(600MHz,DMSO-d6(δ9.32(s,J＝6.9,1.7Hz,1H(,7.77–7.63(m,3H(,7.52(t,J＝7.0Hz,1H(,7.31(td,J＝7.7,3.9Hz,2H(,7.25–7.14(m,4H(,6.36(s,1H(,6.26(s,1H(,5.03(s,2H(,1.90(s,3H(.13C NMR(151MHz,DMSO(δ158.63,154.63,146.33,143.29,135.97,133.28,131.49,131.22,130.68,128.79,128.69,127.64,125.68,125.64,124.01,124.00,121.16,116.61,115.90,115.56,114.94,93.95,44.16,31.66.HRMS(ESI(:Extract mass calculated for C24H18Cl2N2O2[M+H]+:437.08241Found:437.0834.
test example 1 determination of biological Activity of beta-phenylpropenyl-containing pyrido [1,2-a ] pyrimidinone derivatives against housefly
1. Purpose of test
The poisoning activity of 1l-40l of the compound prepared by the invention on houseflies was measured.
2. Test method
The poisoning activity of the compound on the houseflies is measured by adopting a feed mixing method. The mother liquor of the compound to be tested which has been prepared is diluted to a suitable concentration with acetone. 1g of white granulated sugar is weighed and put into a glass tube with the diameter of 2cm and the length of 5cm, 1mL of prepared compound solution to be tested is added into the glass tube, the liquid is not over the white granulated sugar, after the acetone in the glass tube is volatilized, the housefly is stunned by diethyl ether and then put into the glass. The glass tube mouth was sealed with gauze, and each test was repeated three times, 10 houseflies were repeated each time, and the results of the test were averaged over the three results. Then, the glass tube was placed in an artificial climatic chamber at a temperature of 25 (1 ℃ C., relative humidity of 60% to 75%, and light period of L: D=14h: 10h, and death conditions of houseflies were investigated after 24h, respectively. Acetone was set as a blank control group, mortality and corrected mortality were calculated, and according to the results, concentration gradients of the compound series prepared in the examples of the present invention (5 concentrations of the drug solution were measured as described above, mortality and corrected mortality, and correlation coefficient and medium-mortality concentration LC 50 were calculated by using the values of the drug concentration log and the probability of the corrected mortality, respectively. Cinnamaldehyde treatment group was set as a negative control group, and imidacloprid treatment group was set as a positive control group).
3. Test results
The results of activity of the compounds against houseflies are shown in Table 1, and at a concentration of 20. Mu.g/mL, most of the compounds 1l-40l have poisoning effect against houseflies, wherein the mortality rate of houseflies reaches 50% or more after the compounds 26l, 27l, 30l, 34l, 35l and 38l act, and especially reaches 100% after the compounds 26l, 30l, 34l, 35l and 38l act.
Further determination of LC 50 values of compounds against housefly showed that the LC 50 values of compounds 26l, 27l, 30l, 34l and 35l were 3.255. Mu.g/mL, 2.488. Mu.g/mL, 1.512. Mu.g/mL and 1.828. Mu.g/mL, respectively, which were significantly lower than the LC 50 value of imidacloprid, and it was seen that compounds 26l, 27l, 30l, 34l and 35l had very good insecticidal activity against housefly, even better than imidacloprid.
Results of Activity of the compounds of Table 1 against housefly (20. Mu.g/mL [ (]
Note that: the same letter is followed by the same column of data in the table with no significant level of difference (5%).
Results of toxicity measurements of the compounds of Table 2 on housefly
Test example 2 determination of biological Activity of beta-phenylpropenyl-containing pyrido [1,2-a ] pyrimidinone derivatives against Aedes albopictus
1. Purpose of test
The poisoning activity of the compound 1I-40I prepared by the invention on the aedes albopictus larvae is measured.
2. Test method
The poisoning activity of the compound on aedes albopictus larvae is determined by adopting a liquid medicine toxin soaking method, 1mL of prepared mother solution of the compound to be tested is added into a disposable plastic cup, 99mL of overnight tap water is added into each cup, 10 3-year-old larvae with the same size are screened by using a gauze, the 3-year-old larvae are placed into the disposable plastic cup, the disposable plastic cup is placed into an insect-culturing room with the relative humidity of 60% -70% at the temperature of 25 ℃, each group of tests is repeated three times, each 10-year-old larvae are repeated, and the average value of the three results is taken as the test result. And counting the number of dead insects after 24 hours, setting acetone as a blank control group, calculating the death rate and correcting the death rate, and selecting a concentration gradient (5 concentrations of liquid medicine (measured by a method, such as measuring, calculating the death rate and correcting the death rate, and calculating a correlation coefficient and a medium-mortality concentration LC 50 according to the medicinal concentration logarithmic value and the probability value of correcting the death rate) of the compound series prepared by the embodiment of the invention according to the result.
3. Test results
The results of the activity of the compounds on the aedes albopictus larvae are shown in Table 3, and the compounds 1l-40l have poisoning effect on the aedes albopictus larvae at the concentration of 5 mug/mL, wherein the death rate of the aedes albopictus larvae is higher than 50% after the compounds 15l, 17l, 18l, 24l, 26l, 27l, 28l, 29l, 30l, 32l, 34l, 35l, 36l and 38l are acted, and particularly the death rate of the aedes albopictus larvae reaches 100% after the compounds 15l, 26l, 28l, 29l, 34l, 35l and 38l are acted.
Further determination of the LC 50 values of compounds against aedes albopictus larvae, as shown in table 4, the LC 50 values of compounds 26l, 28l, 29l, 34l and 35l were 0.447 μg/mL, 1.622 μg/mL, 1.103 μg/mL, 0.524 μg/mL and 0.745 μg/mL, respectively, which were significantly lower than the LC 50 values of imidacloprid, and it was seen that compounds 26l, 28l, 29l, 34l and 35l had very good biological activity against aedes albopictus larvae, even better than imidacloprid.
Results of Activity of the compounds of Table 3 against Aedes albopictus larvae (5. Mu.g/mL [. Sup.
Note that: the same letter is followed by the same column of data in the table with no significant level of difference (5%).
Toxicity test results of the compounds of Table 4 on Aedes albopictus larvae
Test example 3 determination of biological Activity of beta-phenylpropenyl-containing pyrido [1,2-a ] pyrimidinone derivatives on German cockroach
1. Purpose of test
The poisoning activity of the compound 1I-40I prepared by the invention on the German cockroach is measured.
2. Test method
The poisoning activity of the compounds on the German cockroaches was determined by the spot method. The compound to be tested is diluted by acetone to prepare 1mg/mL of test liquid medicine. After the test insects are stunned by carbon dioxide, the test insects are flatly laid on a filter paper sheet, 1 mu L of test agent is sucked by a microsyringe to be dripped on a chest web, the test insects are placed into a clean 250mL conical flask after acetone is volatilized completely, the bottle mouth is sealed by gauze, the death condition of the German cockroach is counted after the test insects are normally fed for 24 hours, three replicates are arranged in each test, 10 German cockroaches are repeated, and the average value of the results of the three replicates is taken as the test results. Setting acetone as a blank control, calculating the mortality and the correction mortality, and selecting a concentration gradient (5 concentrations of (liquid medicine measured by the method, calculating the mortality and the correction mortality) of the compound series prepared according to the embodiment of the invention according to the result, and calculating a correlation coefficient and a concentration LD 50 in death according to the ratio of the medicine concentration to the correction mortality.
3. Test results
The results of the activity of the compounds on German cockroaches are shown in Table 5, and the compounds 1I-40I have poisoning effect on German cockroaches at a concentration of 1 mug/head (), wherein the mortality rate of the German cockroaches after the compounds 15l, 17l, 26l, 28l, 30l, 34l, 35l and 38l act is higher than 50%, and particularly the mortality rate of the German cockroaches after the compounds 26l, 34l and 35l act reaches 100%.
Further, the LD 50 value of the compound against German cockroach was measured, and the result is shown in Table 6, the LD 50 value of the compound 26l is 0.242 mug/head, which is similar to the LD 50 value of imidacloprid; the LD 50 values of 34l and 35l are respectively 0.142 mug/head and 0.171 mug/head, which are obviously lower than the LD 50 value of the imidacloprid, and the 34l and 35l compounds have very good insecticidal activity on the German cockroach and even are better than the imidacloprid.
Results of the Activity of the compounds of Table 5 on German cockroach (1. Mu.g/head [ ]
Note that: the same letter is followed by the same column of data in the table with no significant level of difference (5%).
Results of toxicity measurements of the compounds of Table 6 on German cockroaches
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310192207.2A CN118580237A (en) | 2023-03-02 | 2023-03-02 | Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310192207.2A CN118580237A (en) | 2023-03-02 | 2023-03-02 | Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118580237A true CN118580237A (en) | 2024-09-03 |
Family
ID=92534257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310192207.2A Pending CN118580237A (en) | 2023-03-02 | 2023-03-02 | Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118580237A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009099929A1 (en) * | 2008-02-06 | 2009-08-13 | E. I. Du Pont De Nemours And Company | Mesoionic pesticides |
| CN110317200A (en) * | 2018-03-28 | 2019-10-11 | 东莞东阳光科研发有限公司 | Pyrimidine compound and application thereof |
| CN113292557A (en) * | 2021-05-31 | 2021-08-24 | 贵州大学 | Pyridopyrimidinone mesoion derivative containing indole unit and preparation method and application thereof |
-
2023
- 2023-03-02 CN CN202310192207.2A patent/CN118580237A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009099929A1 (en) * | 2008-02-06 | 2009-08-13 | E. I. Du Pont De Nemours And Company | Mesoionic pesticides |
| CN110317200A (en) * | 2018-03-28 | 2019-10-11 | 东莞东阳光科研发有限公司 | Pyrimidine compound and application thereof |
| CN113292557A (en) * | 2021-05-31 | 2021-08-24 | 贵州大学 | Pyridopyrimidinone mesoion derivative containing indole unit and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2766672B2 (en) | 4-Amino-3-carboxyquinolines and naphthyridines, production methods and pharmaceutical uses | |
| CN113024561B (en) | Tryptanthrin derivative, preparation thereof and application thereof in preventing and treating plant virus and germ diseases | |
| CN113372276B (en) | Indazole derivatives and their applications | |
| CA2560080A1 (en) | Solifenacin-containing composition | |
| CN112939802A (en) | Ferulic acid amide derivative, and synthesis method and application thereof | |
| CN104530035B (en) | 5-piperonyl-4-alkyl-2-arylaminothiazole and its preparation method and application | |
| Huo et al. | Synthesis and fungicidal evaluation of novel β-carboline-benzimidazole and β-carboline-benzothiazole hybrids | |
| NO834094L (en) | PROCEDURE FOR PREPARING 6,7-DIHYDRO-8- (IMIDAZOL-1-YL) -5-METHYL-1-OXO-1H, 5H-BENZO (IJ) QUINOLIZIN-2-CARBOXYL ACIDS | |
| CN118580237A (en) | Pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl, preparation method and application thereof | |
| CN113278020B (en) | Pityriacitrin alkaloid derivative containing acylthiourea structure and its preparation method and use | |
| CN113402436A (en) | Trolamine derivatives, preparation method and application thereof | |
| CN109721519B (en) | A kind of aryl-substituted thiosemicarbazide compound and its preparation method and application | |
| CN112438272A (en) | Evodiamine analog and application thereof in preventing and treating plant pathogenic fungi | |
| GB2029403A (en) | Hercicidal pyridones and pyridinethiones | |
| CN115160159B (en) | A kind of Halichonine B analog, its preparation method and its application in the preparation of agricultural fungicides | |
| CN113582904B (en) | 5-n-propyl-4-hydroxypyrrol-2-one derivatives and its preparation method and application | |
| CN109516978A (en) | Giantreed alkali derivant and its preparation method and application | |
| CN114380848B (en) | Preparation and application of a kind of isoquinoline thiazole salt and its derivatives | |
| CN115611876A (en) | Novel coumarin derivative containing thiophene and indolyl and synthetic method thereof | |
| CN103141486B (en) | Application of 4-(benzofuran-5-yl)-2-phenzyl aminothiazole as bactericide | |
| CN114716451B (en) | Frutinone compound and preparation method and application thereof | |
| CN105399713A (en) | Novel benzene peptide derivative and preparation method and application thereof | |
| CN116730852B (en) | A class of substituted phenyl isopropanolamine compounds and their preparation method and application | |
| CN106431977B (en) | A kind of unsaturated oximido ethers compound and application thereof | |
| CN104926751A (en) | Benzisothiazolone derivatives and synthetic method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |