Acetic Acid → 4-({[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl}amino)benzonitrile

Participants

Reaction Conditions

Reaction Steps

After the atmosphere in the reaction vessel had been replaced with nitrogen, the suspension containing carbonic acid 2-{3-[(4-cyanophenylamino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester ethyl ester obtained in Example 65 was added at a bath temperature of 15° C., and rinsing in with methanol (2407 mL) and tetrahydrofuran (826 mL). 5 N aqueous sodium hydroxide solution (1599 mL, 7.995 mol) was added dropwise to the mixture at the bath temperature of 15° C., then the bath temperature was set at 20° C., and the reaction suspension was stirred for 16 hours. Thereafter, the bath temperature was set at 15° C., and acetic acid (2288 mL) was added dropwise to the solution obtained. Then, the bath temperature was set at 22° C., and water (3750 mL) was added dropwise. Seed crystals of the captioned compound (374 mg, 0.836 mmol) were added to the mixture which was then stirred for 20 minutes. Then, water (3754 mL) was added dropwise, and the bath temperature was cooled to 0° C. over a period of about 2 hours. Stirring was maintained for 16 hours at the bath temperature of 0° C. The precipitate was filtered, washed with water (2250 mL), and dried under reduced pressure at 40 to 50° C. to obtain the captioned compound (660 g, net weight 631.6 g) as a pale yellow white powder.

Provenance & Evidence