Cesium carbonate → HCID 131732445, compound

Participants

Reaction Conditions

Reaction Steps

To a 5 mL vial were added racemic cis-ethyl 2-(1-(4-bromo-2,6-difluorobenzyl)-6-((3-fluoro-5-methylpyridin-2-yl)methoxy)-1H-benzo[d]imidazol-2-yl)cyclohexanecarboxylate (150 mg, 0.24 mmol), Pd(t-Bu3P)2 (12 mg, 0.024 mmol), 4-fluoropiperidine (28 mg, 0.27 mmol), Cs2CO3 (238 mg, 0.73 mmol) and toluene (1 mL). The mixture was heated at 110° Celsius for 1 h. The mixture was cooled to RT, concentrated to dryness and purified by FCC to afford racemic cis-ethyl 2-(1-(2,6-difluoro-4-(4-fluoropiperidin-1-yl)benzyl)-6-((3-fluoro-5-methylpyridin-2-yl)methoxy)-1H-benzo[d]imidazol-2-yl)cyclohexanecarboxylate. To the resulting ethyl ester, in a 5 mL vial, was added HCl (5 mL, 6 N). The mixture was heated at 100° Celsius for 16 h. The mixture was cooled to RT then concentrated to dryness. The residue was purified using FCC to provide the title compound. MS (ESI): mass calcd. for C33H34F4N4O3, 610.26; m/z found, 611.3 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 6.71 (s, 1H), 6.00-5.97 (m, 1H), 5.95 (d, J=8.8 Hz, 1H), 5.59 (d, J=2.3 Hz, 1H), 5.38 (dd, J=8.8, 2.3 Hz, 1H), 5.07-4.97 (m, 2H), 3.96 (d, J=15.9 Hz, 1H), 3.80 (d, J=15.9 Hz, 1H), 3.68-3.59 (m, 2H), 3.22-3.16 (m, 1H), 2.21-2.15 (m, 1H), 1.93-1.83 (m, 2H), 1.74-1.66 (m, 2H), 1.35-1.28 (m, 1H), 0.87 (s, 3H), 0.83-0.72 (m, 1H), 0.50-0.35 (m, 5H), 0.32-0.14 (m, 4H), 0.01-0.14 (m, 2H).

Provenance & Evidence