7-氯-6-氟-3,4-二氢-1H-喹啉-2-one

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phosphoryl chloride (55.6 cc) is added in the course of 30 minutes, with stirring at between 10° and 15° C. to a mixture of trichloromethane (250 cc) and dimethylformamide (54 cc) and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 7-chloro-6-fluoro-3,4-dihydrocarbostyril (52 g) is added gradually in the course of 10 minutes at approximately 20° C. with vigorous stirring. The suspension obtained is heated to a temperature in the region of 60° C. and kept stirring for a further 2 hours at this temperature. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of water (250 cc) and crushed ice (250 g) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (4×125 cc) at 5° C. The wet product obtained and sodium acetate (58 g) are added simultaneously in the course of 1 hour to water (500 cc) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to approximately 50° C. and the product is drained at this temperature and washed with water (3×250 cc) at approximately 20° C. 2,7-Dichloro-6-fluoro-3-formyl1,4-dihydroquinoline (54.3 g) is obtained in the form of a yellow solid, m.p. 260° C., which is used without further treatment for the subsequent steps. To the solution obtained The suspension obtained is heated to a temperature in the region of 60° C. kept stirring for a further 2 hours at this temperature The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added with vigorous stirring The solid obtained is drained at approximately 5° C. washed with water (4×125 cc) at 5° C The wet product obtained so as to maintain the pH at approximately 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to approximately 50° C. washed with water (3×250 cc) at approximately 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10 and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydro quinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10 and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydro quinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously, in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously, in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phosphoryl chloride (55.6 cc) is added in the course of 30 minutes, with stirring at between 10° and 15° C. to a mixture of trichloromethane (250 cc) and dimethylformamide (54 cc) and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 7-chloro-6-fluoro-3,4-dihydrocarbostyril (52 g) is added gradually in the course of 10 minutes at approximately 20° C. with vigorous stirring. The suspension obtained is heated to a temperature in the region of 60° C. and kept stirring for a further 2 hours at this temperature. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of water (250 cc) and crushed ice (250 g) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (4×125 cc) at 5° C. The wet product obtained and sodium acetate (58 g) are added simultaneously in the course of 1 hour to water (500 cc) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to approximately 50° C. and the product is drained at this temperature and washed with water (3×250 cc) at approximately 20° C. 2,7-Dichloro-6-fluoro-3-formyl1,4-dihydroquinoline (54.3 g) is obtained in the form of a yellow solid, m.p. 260° C., which is used without further treatment for the subsequent steps. To the solution obtained The suspension obtained is heated to a temperature in the region of 60° C. kept stirring for a further 2 hours at this temperature The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added with vigorous stirring The solid obtained is drained at approximately 5° C. washed with water (4×125 cc) at 5° C The wet product obtained so as to maintain the pH at approximately 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to approximately 50° C. washed with water (3×250 cc) at approximately 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10 and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydro quinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously, in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C. which is used in this form for the subsequent steps. close to 20° C obtained The suspension obtained is heated to a temperature close to 60° C. is kept at this temperature for a further 2 hours with stirring The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added, with vigorous stirring The solid obtained is drained at about 5° C. washed with 4 times 125 cm3 of water at 5° C The moist product obtained to maintain the pH at about 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to about 50° C. washed with 3 times 250 cm3 of water at about 20° C

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phosphoryl chloride (55.6 cc) is added in the course of 30 minutes, with stirring at between 10° and 15° C. to a mixture of trichloromethane (250 cc) and dimethylformamide (54 cc) and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 7-chloro-6-fluoro-3,4-dihydrocarbostyril (52 g) is added gradually in the course of 10 minutes at approximately 20° C. with vigorous stirring. The suspension obtained is heated to a temperature in the region of 60° C. and kept stirring for a further 2 hours at this temperature. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of water (250 cc) and crushed ice (250 g) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (4×125 cc) at 5° C. The wet product obtained and sodium acetate (58 g) are added simultaneously in the course of 1 hour to water (500 cc) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 15 minutes at 90° C., the temperature is allowed to fall to approximately 50° C. and the product is drained at this temperature and washed with water (3×250 cc) at approximately 20° C. 2,7-Dichloro-6-fluoro-3-formyl1,4-dihydroquinoline (54.3 g) is obtained in the form of a yellow solid, m.p. 260° C., which is used without further treatment for the subsequent steps. To the solution obtained The suspension obtained is heated to a temperature in the region of 60° C. kept stirring for a further 2 hours at this temperature The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained is added with vigorous stirring The solid obtained is drained at approximately 5° C. washed with water (4×125 cc) at 5° C The wet product obtained so as to maintain the pH at approximately 6 The mixture is stirred for a further 15 minutes at 90° C. to fall to approximately 50° C. washed with water (3×250 cc) at approximately 20° C