Water → 4-amino-6-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylamino)pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-amino-6-chloropyrimidine-5-carbonitrile (0.368 g, 2.381 mmol), 1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine (0.798 g, 2.38 mmol), and DIEA (1.24 mL, 7.14 mmol) in 1-butanol (23.8 mL) was stirred at 120° C. After 23 h, the mixture was removed from the heat and left at rt. After cooling, the mixture was concentrated in vacuo to give a dark purple solid. To the dark purple solid was added water (50 mL) followed by sonication. The resulting precipitate was collected by filtration, washed with water, and air-dried to give the product. The solid 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 a purple solid. The purple solid was suspended in EtOAc-hexane (1:5, 10 mL), filtered, and washed with EtOAc-hexane (1:5, 40 mL) to provide 4-amino-6-(1-(7-bromo-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylamino)pyrimidine-5-carbonitrile as a purple solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47-8.79 (2H, m), 7.88-8.34 (1H, m), 7.67-7.85 (3H, m), 7.44 (1H, dd, J=7.8, 0.8 Hz), 7.22 (3H, t, J=7.9 Hz), 5.29-5.47 (1H, m), 1.57 (3H, d, J=6.8 Hz); LC-MS (ESI) m/z 453.0 [M+H (79Br)]+ and 454.9 [M+H (81Br)]+.

Provenance & Evidence