Morpholine → HCID 71548896, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (1R,2R)-2-((6-((6-iodo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol from Step 2 of Example 96 (150 mg, 0.30 mmol) in DMSO (3 mL) were added morpholine (156 μL, 1.78 mmol), CuI (23 mg, 0.12 mmol), L-proline (14 mg, 0.12 mmol), and K2CO3 (123 mg, 0.89 mmol). The resulting mixture was flushed with argon, the reaction vessel was sealed and the mixture was heated at 100° C. for 2 h, then at 110° C. for 2 h. LCMS analysis showed that the reaction complete. The reaction mixture was cooled to rt, filtered through a Celite plug, and the filtrate was purified by preparative HPLC using a mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-morpholino-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (15 mg, 11%) as a tan powder. 1H NMR (300 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.22 (d, J=2.3 Hz, 1H), 8.03 (d, J=7.2 Hz, 1H), 7.63 (br s, 2H), 7.24-7.34 (m, 1H), 7.14-7.22 (m, 1H), 5.42 (s, 2H), 3.70-3.83 (m, 4H), 3.48-3.55 (m, 2H), 3.07-3.15 (m, 4H), 2.03 (d, J=10.2 Hz, 1H), 1.87 (d, J=9.6 Hz, 1H), 1.61 (br s, 2H), 1.22 (d, J=7.3 Hz, 4H). LCMS (ESI) m/z 465 (M+H)+.

Provenance & Evidence