Pyrrolidine → 1-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-5-(1-pyrrolidinyl-carbonyl)-1H-benzimidazole

Participants

Reaction Steps

Following the general procedure 20E, 1-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carboxylic acid (80 mg, 0.228 mmol) was dissolved in DMF (2 mL) and HATU (104 mg, 0.274 mmol) was added followed by DIPEA (48 μl, 0.274 mmol), After being stirred for 10 min, pyrrolidine was added and the resulting mixture was stirred overnight. The crude residue obtained after work-up was purified using reverse phase preparative HPLC to give a TFA salt as white solids (42 mg, 37%). 1H NMR (400 MHz, CD3OD): δ 8.18 (d, J=2.8 Hz, 1H), 7.98 (d, J=9.2 Hz, 1H), 7.87 (s, 1H), 7.72 (dd, J=9.2 Hz, J=2.0 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.46 (dd, J=9.2 Hz, J=2.8 Hz, 1H), 4.89 (s, 2H), 4.43 (d, J=6.8 Hz, 2H), 4.09 (q, J=7.2 Hz, 2H), 3.60 (t, J=7.6 Hz, 2H), 3.44 (t, J=7.6 Hz, 2H), 2.02–1.94 (m, 2H), 1.92–1.86 (m, 2H), 1.37 (t, J=7.2 Hz, 3H), 1.30–1.22 (m, 1H), 0.64–0.58 (m, 2H), 0.48–0.44 (m, 2H). MS (ESI) (M+H)+=405. Anal. Calcd for C24H28N4O2.0.8TFA.0.2H2O: C, 55.32; H, 5.12; N, 9.49. Found: C, 55.30; H, 4.91; N, 9.23.

Provenance & Evidence