Water → 6-chloro-1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of (1R,2R)-2-((6-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (215 mg, 0.45 mmol), Zn(CN)2 (327 mg, 2.71 mmol), Pd2(dba)3 (82 mg, 0.09 mmol) and dppf (100 mg, 0.18 mmol) in DMA (10 mL) was stirred at 100° C. for 16 h. The reaction mixture was cooled to room temperature, poured into water (20 mL) and extracted with ethyl acetate (50 mL×2). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to give 6-chloro-1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile as a white solid (25 mg, 13.5%). 1H NMR (300 MHz, DMSO-d6): δ 8.69 (s, 1H), 8.36 (s, 1H), 8.13 (s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.45 (s, 1H), 7.16 (s, 1H), 5.53 (s, 2H), 4.68 (d, J=4.5 Hz, 1H), 3.38-3.31 (m, 2H), 1.92-1.86 (m, 2H), 1.65-1.60 (m, 2H), 1.27-1.19 (m, 4H). LCMS (ESI) m/z 422 (M+H)+.

Provenance & Evidence