Heptane → 4-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

Participants

Reaction Steps

A slurry of 4-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidin-2-amine, hydrochloride salt (C9, which can be prepared by the method of J. Sisko, U.S. Pat. No. 6,239,279 B1, May 29, 2001) (200 mg, 0.534 mmol), 2-(chloromethyl)pyrimidine (110 mg, 0.667 mmol) and cesium carbonate (365 mg, 1.12 mmol) in 2-methyltetrahydrofuran (3 mL) and water (1 mL) was heated overnight at 70° C. The resulting solution was cooled, and the organic layer was concentrated in vacuo. Addition of dichloromethane produced a solid; heptane (10 mL) was added, and the resulting mixture was stirred for 10 minutes. Filtration provided the title product as a solid. Yield: 205 mg, 0.476 mmol, 89%. APCI m/z 431.1 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.08-2.14 (m, 4H), 2.30-2.36 (m, 2H), 3.09 (br d, J=12 Hz, 2H), 3.84 (s, 2H), 4.62 (m, 1H), 6.40 (d, J=5.2 Hz, 1H), 7.07 (dd, J=8.8, 8.8 Hz, 2H), 7.39-7.43 (m, 3H), 8.04 (s, 1H), 8.13 (d, J=5.2 Hz, 1H), 8.80 (d, J=5.0 Hz, 2H).

Provenance & Evidence