Patent ID: 9637468
Date: 2017-05-02
CPC Classifications: C07D,C07F

Claim:
1. A process for manufacturing a compound of formula A comprising the steps of: (a) acylating 5-bromo-4-(trifluoromethyl)pyridin-2-amine in a reaction mixture comprising solvents ethyl acetate and heptane, and the acid anhydride acetic anhydride 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 isopropylmagnesium chloride lithium chloride in the solvent tetrahydrofuran followed by an triaklylborate triisopropylborate and 2,2′-azanediyldiethanol in one or more solvents selected from 2-methyltetrahydrofuran or isopropanol to form the boronic ester product, N-(5-(1,3,6,2-dioxazaborocan-2-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide, having the structure  wherein the Boron to Nitrogen bond is a coordinative bond; (c) coupling the boronic ester product, 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 comprising (i.) a catalyst comprising triphenylphosphine and one or more solvents selected from dimethoxyethane, tetrahydrofuran or water, with Pd(OAc) (d) hydrolyzing N-(5-(2,6-dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-yl)acetamide in one or more solvents selected from isopropylacetate or water under acidic conditions to form the compound of formula A.