Cesium carbonate → trans 6-[(2-{2-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-2-methylpyrimidine-4-carbonitrile

Participants

Reaction Steps

2-{2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine from Example 60 Step 1 (50 mg, 0.178 mmol) was in 0.5 mL DMF. Cs2CO3 (290 mg, 0.890 mmol) was added. Reaction mixture was stirred at room temperature for 10 min before cooled to 0° C. in ice bath. 6-chloro-2-methylpyrimidine-4-carbonitrile from Example 5 step 4 (30.1 mg, 0.196 mmol) in 0.3 mL DMF was added via syringe. Reaction was stirred at 0° C. in ice bath for 2 hours. The mixture was quenched with ice water and aqueous phase was further extracted with ethyl acetate for 3 times. The combined organic layers were washed with water and brine, then dried over Na2SO4 and concentrated. The residue was purified by column chromatography eluting with 30% Ethyl acetate/hexane with 0.5% 2M NH3-MeOH to give the titled compound.

Provenance & Evidence