Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluoro-3-methoxyaniline (1.4 g) was added to a chloroform solution (10 ml) with ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate synthesized from ethyl 3-chloro-2,4,5-trifluorobenzoylacetate (2.8 g) in accordance with a method known per se in the art dissolved therein. The reaction mixture was concentrated under reduced pressure, and anhydrous potassium carbonate (2.7 g) and N,N-dimethylformamide (6 ml) were added to the residue, followed by stirring at 90° C. for 15 minutes. The reaction mixture was allowed to cool, and chloroform (80 ml) and distilled water (300 ml) were added to the reaction mixture, thereby conducting liquid separation. A chloroform layer was washed twice with distilled water (300 ml), dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Deposits were dispersed in ethanol, collected by filtration and washed with ethanol and diisopropyl ether in that order to obtain the title compound (2.98 g) as a colorless powder. dissolved The reaction mixture was concentrated under reduced pressure, and anhydrous potassium carbonate (2.7 g) and N,N-dimethylformamide (6 ml) were added to the residue to cool chloroform (80 ml) and distilled water (300 ml) were added to the reaction mixture liquid separation A chloroform layer was washed twice with distilled water (300 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure Deposits were dispersed in ethanol collected by filtration washed with ethanol and diisopropyl ether in that order

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.84 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.75 g of 2-amino-3-fluoro-6-(1,1,3,3-tetramethylbutylamino)pyridine. The solution was concentrated under reduced pressure, and to the residue were added 0.65 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 1 hour and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The precipitate was collected by filtration and washed with ethanol and diisopropylether successively to obtain 0.45 g of the title compound as a pale yellow powder. The solution was concentrated under reduced pressure to the residue were added 0.65 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2.5 ml of chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.70 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 600 mg of 2-amino-3,5-difluoro-6-isopropylaminopyridine. The solution was concentrated under reduced pressure. To the residue were added 600 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 20 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 400 ml of distilled water, and the chloroform layer was washed twice with 400 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 620 mg of the title compound as a pale yellow powder. The solution was concentrated under reduced pressure To the residue were added 600 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 400 ml of distilled water the chloroform layer was washed twice with 400 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.56 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.66 g of 2-amino-5-chloro-3-fluoro-6-(p-methoxybenzylamino)pyridine. The solution was concentrated under reduced pressure. To the residue were added 0.5 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 20 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The solution was allowed to stand after adding 4 ml of ethanol. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 0.56 g of the title compound as a pale yellow powder. The solution was concentrated under reduced pressure To the residue were added 0.5 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure after adding 4 ml of ethanol The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 280 mg of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added all of 2,6-diamino-3-fluoro-5-methylpyridine as described above together with 2 ml of methanol and 4 ml of chloroform. After allowing to stand at room temperature for 40 minutes, the solution was concentrated under reduced pressure. To the residue were added 600 mg of anhydrous potassium carbonate and 1 ml of N,N-dimethylformamide, and the mixture was stirred at 85° C. for 15 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water. The chloroform layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue was added 0.5 ml of ethanol, and the mixture was allowed to stand overnight. The precipitate was dispersed in ethanol, collected by filtration, and washed with ethanol and diisopropylether successively to obtain 171 mg of the title compound as a colorless powder. the solution was concentrated under reduced pressure To the residue were added 600 mg of anhydrous potassium carbonate and 1 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water The chloroform layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure To the residue was added 0.5 ml of ethanol to stand overnight The precipitate was dispersed in ethanol collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.56 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.42 g of 2-amino-6-(t-butylamino)-5-fluoropyridine. The solution was concentrated under reduced pressure to obtain yellow solid residue. To this residue were added 0.6 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 20 minutes and allowed to cool. The solution was separated by adding 40 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, supplemented with 2 ml of ethanol, and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 0.48 g of the title compound as a pale yellow powder. The solution was concentrated under reduced pressure to obtain yellow solid residue to cool The solution was separated by adding 40 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.84 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.65 g of 2-amino-6-(t-butylamino)-3-chloro-5-fluoropyridine. The solution was concentrated under reduced pressure to obtain yellow solid residue. To this residue were added 0.7 g of anhydrous potassium carbonate and 3 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 25 minutes and allowed to cool. The solution was separated by adding 40 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 1.06 g of the title compound as a pale yellow powder. The solution was concentrated under reduced pressure to obtain yellow solid residue to cool The solution was separated by adding 40 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.78 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 2-amino-3,5-difluoro-6-methoxypyridine until completion of the conversion into the aminoacrylate form was confirmed by monitoring the reaction by TLC. The solution was concentrated under reduced pressure, and to the residue were added 0.80 g of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 15 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was collected by filtration, washed with ethanol to obtain 615 mg of the title compound as a pale brown powder. the reaction by TLC The solution was concentrated under reduced pressure to the residue were added 0.80 g of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.78 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.90 g of 2-amino-3,5-difluoro-6-(p-methoxybenzylamino)-4-methylpyridine. The solution was concentrated under reduced pressure, and to the residue were added 1.3 g of anhydrous potassium carbonate and 3 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 15 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the title compound as a brown crude oil. The solution was concentrated under reduced pressure to the residue were added 1.3 g of anhydrous potassium carbonate and 3 ml of N,N-dimethylformamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 5 ml of chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.70 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 430 mg of 2-amino-3,5-difluoro-6-(methylamino)pyridine. The solution was concentrated under reduced pressure. To the residue were added 0.3 g of anhydrous potassium carbonate and 2 ml of N,N-dimethyl-formamide, and the mixture was stirred at 90° C. for 10 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 784 mg of the title compound as a colorless powder. The solution was concentrated under reduced pressure To the residue were added 0.3 g of anhydrous potassium carbonate and 2 ml of N,N-dimethyl-formamide to cool The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water the chloroform layer was washed twice with 300 ml distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was collected by filtration washed with ethanol and diisopropylether successively

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 18 ml of chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 2.52 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 2.65 g of 2-amino-3,5-difluoro-6-(p-methoxybenzylamino)pyridine. The solution was concentrated under reduced pressure, and to the residue were added 2.5 g of anhydrous potassium carbonate and 6 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 15 minutes and allowed to cool. The solution was separated by adding 50 ml of chloroform and 500 ml of distilled water, and the chloroform layer was washed twice with 500 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was dispersed in ethanol, collected by filtration, and washed with ethanol to obtain 3.20 g of the title compound as a yellow powder. The solution was concentrated under reduced pressure to the residue were added 2.5 g of anhydrous potassium carbonate and 6 ml of N,N-dimethylformamide to cool The solution was separated by adding 50 ml of chloroform and 500 ml of distilled water the chloroform layer was washed twice with 500 ml of distilled water dried over anhydrous magnesium sulfate concentrated under reduced pressure The precipitate was dispersed in ethanol collected by filtration washed with ethanol