Acetone → rel-N-cyanomethyl-N-[(1R,3R)-3-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Participants

Reaction Steps

rel-N-[(1R,3R)-3-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (400 mg, 1.18 mmol) was dissolved in acetone (15.0 mL, 204 mmol) and cesium carbonate (576 mg, 1.77 mmol) was added. After 15 min, bromoacetonitrile (130 uL, 1.86 mmol) was added and the mixture stirred at room temperature for 4 days. LCMS analysis showed that the reaction had only gone to 50% completion. A second aliquot of bromoacetonitrile (90.4 uL, 1.30 mmol) was added and the reaction was heated at 45° C. overnight. The reaction was then concentrated under reduced pressure and the residue was taken up in DCM (30 mL) and washed with water (30 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain rel-N-cyanomethyl-N-[(1R,3R)-3-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide as a white foam (261 mg, 58%). LCMS (m/e) 378 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.05 (s, 1H), 5.32 (d, 1H, J=7.3 Hz), 4.34-4.07 (m, 3H), 3.97-3.85 (m, 1H), 3.08 (s, 1H), 2.49-2.39 (m, 1H), 2.17-2.08 (m, 1H), 2.03-1.94 (m, 2H), 1.62-1.45 (m, 3H), 1.30-1.15 (m, 1H).

Provenance & Evidence