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

Participants

Reaction Conditions

Reaction Steps

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 (100 mg, 0.218 mmol) from Example 29, sodium methanesulfinate (90 mg, 0.436 mmol) and unsymmetrical N,N-dimethylethylene diamine (6 mg, 0.066 mmol) in anhydrous DMSO (1 mL) at rt was flushed with a stream of argon for 15 min. To the resulting mixture was added copper (I) trifluoromethane-sulfonate benzene complex (20 mg, 0.0328 mmol). The reaction vessel was sealed and the mixture was heated with stirring at 125° C. for 5 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 (1R,2R)-2-((6-((6-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (12 mg, 12%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.85-8.95 (br m, 2H), 8.61 (s, 1H), 8.02 (d, J=7.3 Hz, 1H), 7.69 (s, 1H), 7.18-7.35 (m, 2H), 5.56 (s, 2H), 4.79 (br s, 1H), 3.25-3.60 (m, 5H), 2.03 (m, 1H), 1.87 (m, 1H), 1.55-1.70 (m, 2H), 1.08-1.36 (m, 4H). LCMS (ESI) m/z 458 (M+H)+.

Provenance & Evidence