Diisopropylethylamine → HCID 86681211, compound

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 6-((5-bromo-7-fluoro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (1.33 g, 3.14 mmol), (1R,2R)-2-aminocyclohexanol (1.09 g, 9.43 mmol), DIEA (1.62 g, 12.58 mmol) and DMA (40 mL) was heated in a sealed vial at 110° C. for 15 h. The mixture was cooled to rt and then partitioned between water and EtOAc. The organic layer was separated and washed sequentially with water and brine. The organic layer was separated, dried over MgSO4, filtered, and concentrated under reduced pressure. The residual solid was purified by trituration with a 6:1 mixture of diethyl ether and DCM to afford (1R,2R)-2-((6-((5-bromo-7-fluoro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (952 mg, 64%) as a tan solid. A 90 mg portion was further purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((5-bromo-7-fluoro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (15 mg) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.52 (s, 1H), 7.98 (d, J=10.0 Hz, 1H), 7.74 (d, J=5.0 Hz, 1H), 7.54 (m, 1H), 7.33 (m, 1H), 7.29 (d, J=10.0 Hz, 1H), 7.08 (m, 1H), 5.52 (s, 2H), 4.75 (d, J=5.0 Hz, 1H), 3.51 (m, 1H), 3.33 (m, 1H), 2.02 (m, 1H), 1.87 (m, 1H), 1.59-1.64 (m, 2H), 1.16-1.30 (m, 4H); LCMS (ESI) m/z 475 and 477 (M+H)+.

Provenance & Evidence