Methanesulfonyl chloride → (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate

Participants

Reaction Steps

To a stirred mixture of (1R,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (517 mg, 1.3 mmol) from Example 162, TEA (194 μL, 1.4 mmol), and CH2Cl2 (15 mL) at rt under argon was added methanesulfonyl chloride (152 μL, 2.0 mmol). After stirring the mixture for 15 h, additional TEA (194 μL, 1.4 mmol) and methanesulfonyl chloride (152 μL, 2.0 mmol) were added. After stirring for an additional 18 h, the mixture was diluted with CH2Cl2 and stirred with saturated aq NaHCO3 (50 mL) for 30 min. The layers were separated and the organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with a gradient of 100% hexanes to 100% EtOAc, to afford (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate (274 mg, 44%) as a clear oil. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.39 (t, J=1.8 Hz, 1H), 8.16 (d, J=7.4 Hz, 1H), 8.04 (dd, J=2.6, 9.5 Hz, 1H), 7.66 (d, J=1.0 Hz, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.22 (dd, J=1.4, 8.2 Hz, 1H), 5.46 (s, 2H), 4.98 (m, 1H), 4.06 (m, 1H), 2.99 (s, 3H), 2.01 (m, 1H), 1.54-1.72 (m, 4H), 1.34-1.50 (m, 3H); LCMS (ESI) m/z 476 (M+H)+.

Provenance & Evidence