Process for Manufacturing 5-(2,6-Di-4-morpholinyl-4-pyrimidinyl)-4-trifluoromethylpyridin-2-amine

摘要

The invention discloses improved processes for manufacturing a compound, 5-(2,6-Di-4-morpholinyl-4-pyrimidinyl)-4-trifluoromethylpyridin-2-amine, its monohydrochloride salt and intermediates thereof.

主权项

1: A process for manufacturing a compound of formula Acomprising the steps of:
(a) acylating 5-bromo-4-(trifluoromethyl)pyridin-2-amine to form N-(5-bromo-4-(trifluoromethyl)pyridin-2-yl)acetamide; (b) reacting N-(5-bromo-4-(trifluoromethyl)pyridin-2-yl)acetamide with an alkyl Grignard reagent followed by an triaklylborate and 2,2′-azanediyldiethanol in an organic solvent to form N-(5-(1,3,6,2-dioxazaborocan-2-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide; (c) coupling N-(5-(1,3,6,2-dioxazaborocan-2-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide with 4,4′-(6-Chloropyrimidine-2,4-diyl)di[morpholine] via a palladium catalyzed Suzuki coupling reaction to form N-(5-(2,6-dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide; and (d) hydrolyzing N-(5-(2,6-dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide under acidic conditions to form the compound of formula A.