Pyridine → (4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine

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Reaction Conditions

Reaction Steps

In a glass pressure vessel, a solution of N-[(4aR,7aR)-6-(5-fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (6 g, 13.6 mmol) in ethanol (240 mL) is treated with pyridine (11 mL). O-methylhydroxylamine hydrochloride (11.4 g, 136.5 mmol) is added and the mixture is heated at 50° C. for 4 hours. The solution is concentrated and diluted with 1 M hydrochloric acid and ethyl acetate. The aqueous layer is separated and neutralized with 50% w/w aqueous solution of sodium hydroxide to adjust the pH to 9. The white precipitate is filtered and dried under vacuum. The crude product is crystallized in hot methyl-t-butyl ether until a complete solution is formed then the solution is cooled to room temperature. The solid precipitate is filtered and dried under vacuum to give the title compound (3.5 g, 76%). ES/MS (m/e): 336 (M+H).

Provenance & Evidence