Morpholine → HCID 86681246, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of (1R,2S,3R)-3-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (262 mg, 0.5 mmol) from Step 5 of Example 232, morpholine (264 μL, 3.0 mmol), L-proline (23 mg, 0.2 mmol), and K2CO3 (209 mg, 1.5 mmol) in DMSO (2.0 mL) was purged with argon for 5 min. Copper (I) iodide (19 mg, 0.02 mmol) was added, and the mixture was purged for an additional 5 min, then heated in a sealed tube at 110° C. for 2 h. The mixture was cooled to rt and filtered through Celite, and the filtrate was 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, followed by silica gel flash chromatography eluting with 5% MeOH in CH2Cl2 to afford (1R,2S,3R)-3-((6-((5-morpholino-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (2 mg, 1%) as a white powder. 1H NMR (500 MHz, MeOH-d4) δ 8.19 (s, 1H), 7.50 (s, 1H), 7.31-7.39 (m, 2H), 7.16-7.23 (m, 2H), 7.05 (dd, J=2.0, 8.9 Hz, 1H), 5.44 (s, 2H), 3.95-4.06 (m, 2H), 3.80-3.88 (m, 4H), 3.50 (dd, J=2.6, 9.2 Hz, 1H), 3.06-3.14 (m, 4H), 2.09 (m, 1H), 1.77-1.86 (m, 2H), 1.48-1.53 (m, 2H), 1.33 (m, 1H); LCMS (ESI) m/z 480 (M+H)+.

Provenance & Evidence