Dichloromethane → US9290457, Example 16

Participants

Reaction Conditions

Reaction Steps

4-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile (intermediate 4)(400 mg, 0.81 mmol) and N-methyl-1H-pyridin-2-one-5-boronic acid pinacol ester (248 mg, 1.06 mmol) are suspended in acetonitrile (15 mL) and are degassed with a stream of argon. Potassium carbonate solution (2 mol/L, 1.22 mL, 2.44 mmol) and 1.1-bis(diphenylphosphino)-ferrocendichloro-palladium(II), complex with dichloromethane (1:1) (6.34 mg, 0.008 mmol) are added and the reaction is stirred at 100° C. overnight. Additional N-methyl-1H-pyridin-2-one-5-boronic acid pinacol ester (100 mg, 0.4 mmol) and 1.1-bis(diphenylphosphino)-ferrocendichloropalladium(II), complex with dichloromethane (1:1) (2 mg, 0.002 mmol) are added and the reaction is continued at 120° C. for 60 min under microwave irradiation. The reaction mixture is filtrated over a layer of silica gel and basic aluminum oxide 1:1 and purified by reversed phase HPLC. Yield: 125 mg; ESI mass spectrum [M+H]+=521; Retention time HPLC: 1.01 min (HPLC method Z018_S04).

Provenance & Evidence