Phosphorus sulfide (P2S5) → 1-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbothioyl)-1h-benzimidazole

Participants

Reaction Conditions

Reaction Steps

To a solution of free base 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbonyl)-1H-benzimidazole (Example 21, from 80 mg 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carboxylic acid) in pyridine (2 mL) was added P2S5 (507 mg, 1.14 mmol). The mixture was heated at 100° C. for 24 h and cooled to room temperature. After being decanted, the supernatant was concentrated and the residue was diluted with EtOAc (20 mL), washed with 1 N NaOH (2×10 mL) and then H2O (2×10 mL). The organic layer was dried over MgSO4 and was evaporated. The crude residue was purified by silica gel column chromatography to give an oil (59 mg, 62% for 2 steps). 1H NMR (400 MHz, CD3OD): δ 7.70 (s, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 6.81 (d, J=8.4 Hz, 2H), 4.27 (s, 2H), 4.08–3.95 (m, 4H), 3.89 (d, J=6.8 Hz, 2H), 3.57 (t, J=7.2 Hz, 2H), 2.14–2.03 (m, 2H), 2.00–1.92 (m, 2H), 1.38 (t, J=7.2 Hz, 3H), 1.06–0.98 (m, 1H), 0.54–0.48 (m, 2H), 0.28–0.22 (m, 2H). MS (ESI) (M+H)+=420.

Provenance & Evidence