Sodium hydride → 5-bromo-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine

Participants

Reaction Steps

To a solution of [(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methanol (S,S-DD3, ent2) (1.1 g, 6.1 mmol) in THF (25 mL) was added sodium hydride (300 mg, 7.4 mmol). The reaction mixture stirred at ambient temperature for 30 minutes. Next, a solution of 5-bromo-4-chloro-2-methylpyrimidine (MM2) (1.5 g, 7.4 mmol) in THF (5 mL) was added and the reaction mixture was stirred at ambient temperature for two hours. Aqueous sodium bicarbonate (20 mL) was carefully added and the mixture was extracted with EtOAc (2×50 mL). The combined organics were dried over MgSO4, filtered and concentrated to afford the title compound as a yellow oil, which was sufficiently pure to use in the subsequent step without further purification. 1H NMR (500 MHz, DMSO): δ 8.60 (s, 1 H), 8.12 (d, J=3.0 Hz, 1 H), 7.30-7.22 (m, 2 H), 4.42 (d, J=7.1 Hz, 2 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.19 (dt, J=8.6, 4.6 Hz, 1 H), 1.75 (s, 1 H), 1.14 (dt, J=8.8, 4.7 Hz, 1 H), 1.04 (dt, J=8.9, 4.7 Hz, 1 H); LRMS m/z (M+H) 350.3 found, 350.2 required.

Provenance & Evidence