Phosgene → N,N-Dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl}-4-nitrobenzamide

Participants

Reaction Conditions

Reaction Steps

Ethyl acetate (16 ml) and 2-amino-4,6-dimethoxypyrimidine (5.0 g, 32.2 mmol) were introduced and cooled to −10° C. under nitrogen. Phosgene (5.1 g, 51.5 mmol) was passed in at this temperature and a solution of triethylamine (6.5 g, 64.2 mmol) in ethyl acetate (20 ml) was added dropwise in the course of 1 hour. After 1 hour, the reaction was warmed to 20° C. and nitrogen was blown through until it no longer contained phosgene, and then N,N-dimethyl-2-aminosulfonyl-4-nitrobenzamide (8.1 g, 29.6 mmol) was added. The mixture was cooled to −10° C. and a solution of triethylamine (3.3 g, 32.7 mmol) in ethyl acetate (15 ml) was added dropwise in the course of 60 minutes, and the mixture was stirred for 30 minutes and warmed to room temperature. Potassium hydroxide solution (1.0M, 100 ml) was then added, the phases were separated and the aqueous phase was extracted with ethyl acetate. The aqueous phase was adjusted to pH=2 using 6M hydrochloric acid, and the product was filtered off, washed with water (2×20 ml) and dried. Yield: 10.28 g, 72.6% of theory.

Provenance & Evidence