Phosphorus oxychloride → cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholine

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Reaction Conditions

Reaction Steps

To solid 2-(cis-2,6-dimethylmorpholino)-5-(2-methylpyridin-4-yl)pyrimidin-4-ol (8.3 g, 27.6 mmol) at 20° C. was added neat phosphorus oxychloride (79 ml, 848 mmol). The reaction mixture was stirred at 110° C. for 3 hours. After cooling to 30° C., most of the phosphorus oxychloride was removed and 20 ml of dichloromethane was added. The solution was added into ice-water. The pH was adjusted to 8 using sodium bicarbonate. The dichloromethane layer was separated, washed with water, dried and evaporated. The crude product was added to a silica gel column and was eluted with dichloromethane and then dichloromethane/methanol (5:1). Collected fractions were evaporated to give the title compound (680 mg, 1.960 mmol, 7.09% yield). LC/MS [M+H]+=319/321.

Provenance & Evidence