Dimethylformamide → 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of (1R,2R)-2-((6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (100 mg, 0.218 mmol) from Example 78, zinc cyanide (77 mg, 0.654 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (18 mg, 0.0327 mmol) in anhydrous DMF (2 mL) at rt was purged for 15 min with a stream of argon. To the resulting mixture was added tris(dibenzylideneacetone)dipalladium (18 mg, 0.0218 mmol). The reaction vessel was sealed and the mixture was stirred at 100° C. for 2 h. After cooling to rt, the reaction mixture was purified directly by reverse-phase 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 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-5-carbonitrile (34 mg, 39%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.34 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.3 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.67 (d, J=1.1 Hz, 1H), 7.32 (m, 1H), 7.22 (m, 1H), 5.53 (s, 2H), 4.77 (br s, 1H), 3.51 (m, 1H), 3.30 (m, 1H), 2.03 (m, 1H), 1.85 (m, 1H), 1.65-1.67 (m, 2H), 1.08-1.37 (m, 4H). LCMS (ESI) m/z 405 (M+H)+.

Provenance & Evidence