Water → (1R,2R)-2-((6-((6-chloroimidazo[1,2-b]pyridazin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-((6-chloroimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (1.0 g, 2.7 mmol), (1R,2R)-2-aminocyclohexanol (0.93 g, 8.1 mmol) and DIEA (697 mg, 5.4 mmol) in NMP (40 mL) was stirred for 2 d at 140° C. The mixture was cooled to rt and water (150 mL) was added. The mixture was extracted with EtOAc (100 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 50:1 to 10:1 DCM/MeOH to afford (1R,2R)-2-((6-((6-chloroimidazo[1,2-b]pyridazin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a brown solid (530 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 8.20 (d, J=9.6 Hz, 1H), 7.86 (d, J=7.2 Hz, 1H), 7.63 (s, 1H), 7.54 (d, J=1.8 Hz, 1H), 7.32 (d, J=9.9 Hz, 1H), 7.27 (d, J=1.8 Hz, 1H), 7.12 (dd, J=1.5, 8.4 Hz, 1H), 4.73 (d, J=5.1 Hz, 1H), 4.29 (s, 2H), 3.52-3.49 (m, 1H), 3.39-3.36 (m, 1H), 2.05-2.01 (m, 1H), 1.90-1.86 (m, 1H), 1.65-1.59 (m, 2H), 1.30-1.16 (m, 4H). LCMS (ESI) m/z 414 (M+H)+.

Provenance & Evidence