N-amino-N-methylformamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydro-benzo[b][1,8]naphthpyridine is prepared under the conditions of Example 1 but starting from 19.25 g of ethyl 2-(2,7-dichloro-6-fluoroquinoline-3-carbonyl)-3-dimethylaminoacrylate, 4.05 g of N-formyl-N-methylhydrazine and 1.6 g of DBU in 200 cm3 of ethanol. 16.4 g of 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methyl-amino)-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine are obtained in the form of a colorless solid melting at 296°-298° C., which is used for the subsequent steps without further purification.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydrobenzo [b][1,8]naphthyridine is prepared under the conditions described in Example 1 but starting from 19.25 g of ethyl 2-(2,7-dichloro-6-fluoroquinoline-3-carbonyl)-3-dimethylaminoacrylate, 4.05 g of N-formyl-N-methylhydrazine and 1.6 g of DBU in 200 cm3 of ethanol. 16.4 g of 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihy drobenzo [b][1,8]naphthyridine are obtained in the form of a colourless solid melting at 296°-298° C. The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydrobenzo [b][1,8]naphthyridine is prepared under the conditions

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydrobenzo [b][1,8]naphthyridine is prepared under the conditions described in Example 1 but starting from 19.25 g of ethyl 2-(2,7-dichloro-6-fluoroquinoline-3-carbonyl)-3-dimethylaminoacrylate, 4.05 g of N-formyl-N-methylhydrazine and 1.6 g of DBU in 200 cm3 of ethanol. 16.4 g of 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihy drobenzo [b][1,8]naphthyridine are obtained in the form of a colourless solid melting at 296°-298° C. The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydrobenzo [b][1,8]naphthyridine is prepared under the conditions

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine is prepared under the conditions of Example 1 but starting from 19.25 g of ethyl 2-(2,7-dichloro-6-fluoroquinoline-3-carbonyl)-3-dimethylaminoacrylate, 4.05 g of N-formyl-N-methylhydrazine and 1.6 g of DBU in 200 cm3 of ethanol. 16.4 g of 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine are obtained in the form of a colourless solid melting at 296°-298° C., which can be used for the subsequent steps without further purification. The 8-chloro-3-ethoxycarbonyl-7-fluoro-1-(N-formyl-N-methylamino)-4-oxo-1,4-dihydro-benzo[b][1,8]naphthyridine is prepared under the conditions of Example 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.8 g of 1-formyl-1-methylhydrazine are added dropwise to a solution of 16 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-ethoxy-acrylate in 60 ml of ethanol, while cooling with ice and stirring. The mixture is stirred at room temperature for 1 hour, 60 ml of water are added, the mixture is cooled with ice and the precipitate is filtered off with suction and washed with water/ethanol (1:1). 12 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-(2-formyl-2-methylhydrazino)-acrylate of melting point 92° C. are obtained. while cooling with ice The mixture is stirred at room temperature for 1 hour the mixture is cooled with ice the precipitate is filtered off with suction washed with water/ethanol (1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.8 g of 1-formyl-1-methylhydrazine are added dropwise to a solution of 16 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-ethoxy-acrylate in 60 ml of ethanol, while cooling with ice and stirring. The mixture is stirred at room temperature for 1 hour, 60 ml of water are added, the mixture is cooled with ice and the precipitate is filtered off with suction and washed with water/ethanol (1:1). 12 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-(2-formyl-2-methylhydrazino)-acrylate of melting point 92° C. are obtained. while cooling with ice The mixture is stirred at room temperature for 1 hour the mixture is cooled with ice the precipitate is filtered off with suction washed with water/ethanol (1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.8 g of 1-formyl-1-methylhydrazine are added dropwise to a solution of 16 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-ethoxy-acrylate in 60 ml of ethanol, while cooling with ice and stirring. The mixture is stirred at room temperature for 1 hour, 60 ml of water are added, the mixture is cooled with ice and the precipitate is filtered off with suction and washed with water/ethanol (1:1). 12 g of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-(2-formyl-2-methylhydrazino)-acrylate of melting point 92° C. are obtained. while cooling with ice The mixture is stirred at room temperature for 1 hour the mixture is cooled with ice the precipitate is filtered off with suction washed with water/ethanol (1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 39.24 g (0.4 mol) of propiolic acid ethyl ester were added to a solution of 29.63 g (0.4 mol) of N-amino-N-methylformamide in 80 ml of dioxane and left standing for 3 weeks at room temperature. The yellow solution was evaporated at 40° C./30 torr and the residue filtered over a silical gel column (350 g) with a mixture of dichloromethane/n-hexane 49:1 in fractions of 250 ml each. Fractions 2 to 10 were united and evaporated at 40° C./30 torr, yielding 63.9 g (93%) of 3-(formylmethylhydrazono)-propionic acid ethyl ester as a yellow fluid (IR: 3462, 2984, 1735, 1688, 1629, 1183, 1045 cm-1). left standing for 3 weeks at room temperature The yellow solution was evaporated at 40° C./30 torr the residue filtered over a silical gel column (350 g) with a mixture of dichloromethane/n-hexane 49:1 in fractions of 250 ml each evaporated at 40° C./30 torr

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1.81 g (10 mmol) of dicyclohexylamine was added to a solution of 0.98 g (10 mmol) of propiolic acid ethyl ester in 4 ml of toluene, and the mixture was stirred for 6 hours at room temperature. The resulting yellow solution of 3-(dicyclohexylamino) acrylic acid ethyl ester was heated to 100° C., 0.98 g (9.6 mmol) of triethylaimine were added and the mixture heated to reflux. With stirring a solution of 1.93 g (9.1 mmol) of 2,3,4,5-tetrafluorobenzoic acid chloride in 10 ml of toluene was added in the course of 10 min. The brown suspension was filtered hot and the filter residue washed twice with 15 ml of toluene. The united filtrates containing the so formed 3-(dicyclohexyl-amino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester were stirred for 160 hours at room temperature with 7.41 g (100 mmol) of N-amino-N-methylformamide. The resulting brown suspension was dissolved in 200 ml of dichloromethane, extracted with 50 ml of 1N aqueous hydrochloric acid, and the aqueous extracts washed twice with each 50 ml of dichloromethane. The organic phases were united, dried over magnesium sulphate, filtered and evaporated at 45° C./30 torr. The light-brown, oily residue (4.65 g) was suspended in 10 ml of tert.-butyl methyl ether, digested intensely for 30 min., the crystals filtered, washed twice with each 5 ml of tert.-butyl methyl ether and dried at 25° C./33 torr. There were obtained 1.91 g (64%) of 3-(2-formyl-2-methylhydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester as a white powder of mp 189°. 0.98 g (9.6 mmol) of triethylaimine were added the mixture heated to reflux was added in the course of 10 min The brown suspension was filtered hot the filter residue washed twice with 15 ml of toluene The united filtrates containing the so formed 3-(dicyclohexyl-amino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester extracted with 50 ml of 1N aqueous hydrochloric acid the aqueous extracts washed twice with each 50 ml of dichloromethane dried over magnesium sulphate filtered evaporated at 45° C./30 torr digested intensely for 30 min. the crystals filtered washed twice with each 5 ml of tert.-butyl methyl ether dried at 25° C./33 torr

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1.81 g (10 mmol) of dicyclohexylamine was added to a solution of 0.98 g (10 mmol) of propiolic acid ethyl ester in 4 ml of toluene, and the mixture was stirred for 6 hours at room temperature. The resulting yellow solution of 3-(dicyclohexylamino) acrylic acid ethyl ester was heated to 100° C., 0.98 g (9.6 mmol) of triethylaimine were added and the mixture heated to reflux. With stirring a solution of 1.93 g (9.1 mmol) of 2,3,4,5-tetrafluorobenzoic acid chloride in 10 ml of toluene was added in the course of 10 min. The brown suspension was filtered hot and the filter residue washed twice with 15 ml of toluene. The united filtrates containing the so formed 3-(dicyclohexyl-amino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester were stirred for 160 hours at room temperature with 7.41 g (100 mmol) of N-amino-N-methylformamide. The resulting brown suspension was dissolved in 200 ml of dichloromethane, extracted with 50 ml of 1N aqueous hydrochloric acid, and the aqueous extracts washed twice with each 50 ml of dichloromethane. The organic phases were united, dried over magnesium sulphate, filtered and evaporated at 45° C./30 torr. The light-brown, oily residue (4.65 g) was suspended in 10 ml of tert.-butyl methyl ether, digested intensely for 30 min., the crystals filtered, washed twice with each 5 ml of tert.-butyl methyl ether and dried at 25° C./33 torr. There were obtained 1.91 g (64%) of 3-(2-formyl-2-methylhydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester as a white powder of mp 189°. 0.98 g (9.6 mmol) of triethylaimine were added the mixture heated to reflux was added in the course of 10 min The brown suspension was filtered hot the filter residue washed twice with 15 ml of toluene The united filtrates containing the so formed 3-(dicyclohexyl-amino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester extracted with 50 ml of 1N aqueous hydrochloric acid the aqueous extracts washed twice with each 50 ml of dichloromethane dried over magnesium sulphate filtered evaporated at 45° C./30 torr digested intensely for 30 min. the crystals filtered washed twice with each 5 ml of tert.-butyl methyl ether dried at 25° C./33 torr

Conditions: temp:0.00; pressure:0.00; stir: