Sulfuryl chloride → N-((1R,2R)-2-chlorocyclohexyl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine

Participants

Reaction Steps

To a stirred mixture of (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (282 mg, 0.7 mmol) from Example 162, DIEA (247 μL, 1.4 mmol), and CH2Cl2 (15 mL) at 0° C. under argon was added sulfuryl chloride (142 mg, 2.0 mmol). The mixture was warmed to rt and stirred for 15 h, and then stirred at 60° C. for 15 h. The mixture was cooled to rt and purified directly by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase. The product was further purified by triturating in CH2Cl2 (5 mL) to afford N-((1R,2R)-2-chlorocyclohexyl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine (29 mg, 10%) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.68 (s, 1H), 8.41 (s, 1H), 8.24 (d, J=8.4 Hz, 1H), 8.07 (dd, J=2.6, 9.5 Hz, 1H), 7.68 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 7.24 (dd, J=1.4, 8.2 Hz, 1H), 5.48 (s, 2H), 4.02 (m, 1H), 3.87 (m, 1H), 2.20 (m, 1H), 2.07 (m, 1H), 1.63-1.75 (m, 3H), 1.29-1.41 (m, 3H); LCMS (ESI) m/z 416 (M+H)+.

Provenance & Evidence