Dichloromethane → (1R,2R)-2-((6-((6-vinyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (200 mg, 0.44 mmol) from Example 29 in n-PrOH were added potassium vinyltrifluoroborate (117 mg, 0.88 mmol), PdCl2(dppf).DCM (18 mg, 0.022 mmol), and TEA (122 μL, 0.88 mmol). The resulting mixture was purged with argon for 5 min, the reaction vessel was sealed and the mixture was heated at 100° C. overnight. LCMS analysis showed that the reaction was complete. The reaction mixture was cooled to rt and purified 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 to afford (1R,2R)-2-((6-((6-vinyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a tan powder (40 mg, 23%). 1H NMR (300 MHz, MeOH-d4) δ 8.50 (d, J=1.7 Hz, 1H), 8.43 (s, 1H), 8.15 (d, J=1.7 Hz, 1H), 7.63 (s, 1H), 7.32-7.41 (m, 1H), 7.25-7.32 (m, 1H), 6.91 (dd, J=10.9, 17.7 Hz, 1H), 5.91 (d, J=17.5 Hz, 1H), 5.53 (s, 2H), 5.35 (d, J=11.1 Hz, 1H), 3.50-3.66 (m, 1H), 3.37-3.49 (m, 1H), 2.14 (d, J=12.1 Hz, 1H), 2.01 (br s, 1H), 1.63-1.82 (m, 2H), 1.13-1.50 (m, 4H). LCMS (ESI) m/z 406 (M+H)+.

Provenance & Evidence