Cyanoacetamide → tert-Butyl [3-(7-amino-6-carbamoyl-2-chloro-5-oxo-5H-pyrido[2,3-d]pyrimidin-8-yl)propyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution, cooled to 2-5°C. on an ice bath, of 1.21 g (14.39 mmol) of cyanoacetamide in 20 mL of anhydrous DMF are added portionwise 1.73 g (43.17 mmol) of 60% sodium hydride. The mixture is stirred for 15 minutes at 2-5°C., and this suspension is then added rapidly to the solution of 4.56 g (13.70 mmol) of the acid fluoride prepared in step 11.2 in 30 mL of anhydrous DMF, precooled to 2-5°C. on an ice bath. The mixture is stirred overnight at room temperature and then cooled to 2-5°C., and a further 0.22 g of 60% sodium hydride is added. The medium is stirred overnight at room temperature, and ice is then added slowly to destroy the excess hydride, and the reaction mixture is poured into an ice-water mixture. The resulting mixture is acidified by adding aqueous 1 N HCl solution. The precipitate formed is isolated by filtration, rinsed with water and then dried. The expected product is obtained in the form of an orange solid, which is used as obtained in the following step. Yield=64%.

Provenance & Evidence