N,N-二甲基丁胺

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

实验步骤: To a solution of (2E)-3-{1-[bis(4-fluorophenyl)methyl]-3-cyano-4,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-2-yl}prop-2-enoic acid (200 mg, 0.451 mmol) in THF (2 ml) were added DMF (0.020 ml) and oxalylchloride (0.0471 ml, 0.540 mmol), the mixture was stirred at room temperature for 1 hour and the solvent was distilled off under reduced pressure. The residue was added under ice-cooling to a solution of dimethylbutylamine (121 mg, 0.900 mmol), triethylamine (0.251 ml, 1.80 mmol) and THF (2 ml), and the mixture was stirred under ice-cooling for 2 hours and at room temperature for 12 hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from hexane and ethyl acetate. Yield (amount) 190 mg, yield (rate) 74.1% the solvent was distilled off under reduced pressure The residue was added under ice- the mixture was stirred under ice- cooling for 2 hours and at room temperature for 12 hours extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was recrystallized from hexane and ethyl acetate Yield (amount) 190 mg yield (rate) 74.1%

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 2 L reactor system 543.27 g of 3-chloro-1,2-dihydroxypropane (99.6%, 4.90 moles) is added to 721.03 g of distilled water. The solution is brought to 25° C. Over 45 minutes 479.54 g dimethylbutylamine (99.5%, 4.72 moles) is added to the reactor. After one hour of mixing the temperature is increased to 40° C. and held for one hour. The temperature is then increased to 50° C. and held for 2.5 hours. The temperature is then increased to 60° C. and held for one hour. External heating is turned off and the reaction solution is allowed to stir overnight (16 hours). The pH is then increased to 10.6 by adding 3.52 g sodium hydroxide (50%) and the temperature is increased to 40° C. After 30 minutes, 2.89 g sodium hydroxide (50%) is added to increase the pH from 9.9 to 10.7. After 30 additional minutes, 2.96 g of sodium hydroxide (50%) is added to increase the pH from 9.4 to 10.7. 6.84 g of 3-chloro-1,2-dihydroxypropane is then added and the solution is allowed to stir at room temperature for 60 hours. 11.39 g of trimethylamine (43.6%) and 1.80 g sodium hydroxide (50%) is then added. The solution is allowed to stir overnight (16 hours) at room temperature. The solution was then heated to 40° C. and purged with nitrogen to remove the excess trimethylamine. The solution is cooled to room temperature, the pH was adjusted to 6.9 and it is filtered through Whatman 42 filter paper. The isolated product has the following structure: is brought to 25° C After one hour of mixing the temperature The temperature is then increased to 50° C. held for 2.5 hours The temperature is then increased to 60° C. held for one hour External heating The pH is then increased to 10.6 the temperature is increased to 40° C After 30 minutes to increase the pH from 9.9 to 10.7 to increase the pH from 9.4 to 10.7 to stir at room temperature for 60 hours to stir overnight (16 hours) at room temperature The solution was then heated to 40° C. purged with nitrogen to remove the excess trimethylamine The solution is cooled to room temperature is filtered through Whatman 42 filter paper

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

实验步骤: To a solution of (2E)-3-{1-[bis(4-fluorophenyl)methyl]-3-cyano-4,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-2-yl}prop-2-enoic acid (200 mg, 0.451 mmol) in THF (2 ml) were added DMF (0.020 ml) and oxalylchloride (0.0471 ml, 0.540 mmol), the mixture was stirred at room temperature for 1 hour and the solvent was distilled off under reduced pressure. The residue was added under ice-cooling to a solution of dimethylbutylamine (121 mg, 0.900 mmol), triethylamine (0.251 ml, 1.80 mmol) and THF (2 ml), and the mixture was stirred under ice-cooling for 2 hours and at room temperature for 12 hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from hexane and ethyl acetate. Yield (amount) 190 mg, yield (rate) 74.1% the solvent was distilled off under reduced pressure The residue was added under ice- the mixture was stirred under ice- cooling for 2 hours and at room temperature for 12 hours extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was recrystallized from hexane and ethyl acetate Yield (amount) 190 mg yield (rate) 74.1%

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 2 L reactor system 543.27 g of 3-chloro-1,2-dihydroxypropane (99.6%, 4.90 moles) is added to 721.03 g of distilled water. The solution is brought to 25° C. Over 45 minutes 479.54 g dimethylbutylamine (99.5%, 4.72 moles) is added to the reactor. After one hour of mixing the temperature is increased to 40° C. and held for one hour. The temperature is then increased to 50° C. and held for 2.5 hours. The temperature is then increased to 60° C. and held for one hour. External heating is turned off and the reaction solution is allowed to stir overnight (16 hours). The pH is then increased to 10.6 by adding 3.52 g sodium hydroxide (50%) and the temperature is increased to 40° C. After 30 minutes, 2.89 g sodium hydroxide (50%) is added to increase the pH from 9.9 to 10.7. After 30 additional minutes, 2.96 g of sodium hydroxide (50%) is added to increase the pH from 9.4 to 10.7. 6.84 g of 3-chloro-1,2-dihydroxypropane is then added and the solution is allowed to stir at room temperature for 60 hours. 11.39 g of trimethylamine (43.6%) and 1.80 g sodium hydroxide (50%) is then added. The solution is allowed to stir overnight (16 hours) at room temperature. The solution was then heated to 40° C. and purged with nitrogen to remove the excess trimethylamine. The solution is cooled to room temperature, the pH was adjusted to 6.9 and it is filtered through Whatman 42 filter paper. The isolated product has the following structure: is brought to 25° C After one hour of mixing the temperature The temperature is then increased to 50° C. held for 2.5 hours The temperature is then increased to 60° C. held for one hour External heating The pH is then increased to 10.6 the temperature is increased to 40° C After 30 minutes to increase the pH from 9.9 to 10.7 to increase the pH from 9.4 to 10.7 to stir at room temperature for 60 hours to stir overnight (16 hours) at room temperature The solution was then heated to 40° C. purged with nitrogen to remove the excess trimethylamine The solution is cooled to room temperature is filtered through Whatman 42 filter paper