Morpholine → 1-(Cyclohexylmethyl)-2-(1,1-dimethylpropyl)-5-(morpholin-4-ylcarbonyl)-1H-benzimidazole

Participants

Reaction Steps

Following the same procedure in Example 3, Step A, using morpholine (26.1 mg, 0.30 mmol), diisopropylethylamine (69.7 μL, 51.7 mg, 0.40 mmol) and a solution of 1-(cyclohexylmethyl)-2-(1,1-dimethylpropyl)-1H-benzimidazole-5-carboxylic acid (65.7 mg, 0.20 mmol)) (for preparation, see in Example 4, Step E) in DMF (5 mL) at 0° C., and later, HATU (91.3 mg, 0.24 mmol). The mixture was stirred overnight at room temperature, added H2O (50 mL), extracted with EtOAc (3×50 mL). The desired title compound was purified by reversed-phase HPLC (C-18 column) using 10-50% CH3CN/H2O to give 82.1 mg (80%) of a white solid. 1H NMR (400 MHz, CD3OD): δ 0.86 (t, J=7.42 Hz, 3 H), 1.27 (m, 5 H), 1.65 (m, 3 H), 1.69 (s, 6 H), 1.78 (m, 2 H), 2.04 (q, J=7.42 Hz, 2 H), 2.12 (m, 1 H), 3.47 (m, 2 H), 3.62 (m, 2 H), 3.79 (m, 4 H), 4.50 (d, J=7.62 Hz, 2 H), 7.66 (dd, J=8.69, 1.46 Hz, 1 H), 7.82 (d, J=0.78 Hz, 1 H), 8.01 (d, J=8.79 Hz, 1 H). MS (ESI) (M+H)+=398.3. Anal. Calcd for C24H35N3O2+1.60 TFA+1.10 H2O+0.30 MeCN (612.14): C, 54.55; H, 6.54; N, 7.55. Found: C, 54.61; H, 6.53; N, 7.51.

Provenance & Evidence