Sodium hydride → 2-methyl-6-(2-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyrimidine-4-carbonitrile

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Reaction Steps

NaH (60%, 18 mg, 0.45 mmol, 1.2 eq) was placed in a 1 dram vial and DMF (1.2 mL) added. A solution of 2-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (100 mg, 0.375 mmol) was added dropwise (0.5 mL) to the slurry, and the mixture stirred at RT for 10 min. The solution was cooled to −20° C., and a solution of 6-chloro-2-methylpyrimidine-4-carbonitrile (115 mg, 0.75 mmol) in DMF (0.5 mL) was added drop-wise. The red mixture was stirred for 40 minutes. A solution of ice-cold saturated NH4Cl (aq., 1 mL) was added, and the mixture diluted with EtOAc (100 mL) and water (50 mL). The mixture was transferred to a separatory funnel, the mixture shaken, and the layers separated. The organic fraction was washed with water (20 mL), dried over MgSO4, filtered, and concentrated in vac. The red oil was purified by chromatography on silica gel 1:7 EtOAc:Hexanes to give the title compound.

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