Diisopropylethylamine → 4-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-N-cyclopropylmorpholine-2-carboxamide

Participants

Reaction Steps

2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (0.95 g, 2.35 mmol) was added to a solution of N-cyclopropylmorpholine-2-carboxamide (0.8 g, 2.6 mmol) (see following steps B and C for preparation) and DIPEA (0.82 mL, 4.7 mmol) in DCE (80 mL) at 80° C. The reaction mixture was stirred for 1 h and the solvent was concentrated. The product was purified by MPLC on silica gel using 60-90% EtOAc/Heptane to provide the title compound as white solid. Yield: 1.1 g (71%); 1H NMR (400 MHz, CDCl3) δ 0.39-0.54 (m, 2 H), 0.69-0.80 (m, 2 H), 1.49-1.69 (m, 3 H), 1.72 (s, 9 H), 1.75-1.86 (m, 3 H), 2.09 (t, J=10.84 Hz, 1 H), 2.2 (m, 3 H), 2.38-2.50 (m, 1 H), 2.61-2.71 (m, 1 H), 3.56 (d, J=11.91 Hz, 1 H), 3.67 (td, J=11.52, 1.95 Hz, 1 H), 3.91-4.06 (m, 3 H), 4.44 (d, J=7.03 Hz, 2 H), 6.58 (d, J=3.12 Hz, 1 H), 7.63-7.73 (m, 2 H), 8.04 (s, 1 H); MS (ESI) (M+H)+=538.8; Anal. Calcd for C26H36F2N4O4S+2.2 TFA: C, 46.25; H, 4.88; N, 7.10. Found: C, 46.26; H, 5.00; N, 6.95.

Provenance & Evidence