Hydrochloric Acid → 1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine

Participants

Reaction Steps

A solution of N-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethyl)acetamide (1.5652 g, 4.15 mmol) and 2N HCl (31.1 mL, 62.2 mmol) was heated at 100° C. After 6 h, the mixture was cooled to rt and partitioned between DCM (50 mL) and water (50 mL). The acidic aqueous mixture was washed with DCM (50 mL×4) to remove organic impurities and then basified to ˜pH 12 with 10N NaOH (6 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with water (100 mL×1), brine (100 mL×1), dried over MgSO4, filtered, and concentrated in vacuo to give a dark red syrup. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep™ pre-packed silica gel column (80 g), eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide 1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine as a brown syrupy solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.86 (1H, t, J=2.8 Hz), 8.73 (1H, dt, J=13.5, 1.4 Hz), 8.23-8.33 (1H, m), 7.75 (1H, dd, J=8.0, 1.0 Hz), 7.41 (1H, d, J=7.4 Hz), 7.21 (1H, t, J=7.9 Hz), 3.76 (1H, q, J=6.7 Hz), 1.93 (2H, br. s.), 1.36 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 334.9 [M+H (79Br)]+ and 337 [M+H (81Br)]+.

Provenance & Evidence