Thiophosgene → Methyl 4-{[(4-tert-butylcyclohexyl)(5-methoxy-1-methyl-1h-benzimidazol-2-yl)amino]methyl}benzoate

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Reaction Steps

To a solution of the title compound of Example 1 Step B (2.5 mmol, 759 mg) and DIEA (3 mmol, 0.52 mL) in 10 mL of DCM was added thiophosgene (2.5 mmol, 0.19 mL) (exothermic). After 15 min the title compound of Example 14 Step B (3 mmol, 456 mg) and DIEA (3 mmol, 0.52 mL) were added to the solution. After 30 min Hg(O2CCF3)2 (2.5 mmol, 1.1 g) was added (exothermic), resulting in formation of an orange precipitate. After 30 min the solution was poured into NaHCO3 (aq) containing Na2S, and the slurry was filtered through celite, and the filter cake was washed with DCM. The organic phase was collected and the aqueous phase was extracted with 2×DCM. The combined organic phase was dried with Na2SO4 and concentrated under reduced pressure affording a tan solid. Purification by flash chromatography on silica eluting with 25% EtOAc/hexanes afforded the product as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.92 (d, 2H), 7.45 (d, 2H), 7.20 (d, 1H), 7.08 (d, 1H), 6.84 (dd, 1H), 4.63 (s, 2H), 3.90 (s, 3H), 3.86 (s, 3H), 3.18 (m, 1H), 2.11 (m, 2H), 1.90 (m, 2H), 1.60 (m, 2H), 0.96-1.15 (overlapping m, 3H), 0.87 (s, 9H). MS (ESI): m/z 464 (M+H). HPLC A: 2.45 min.

Provenance & Evidence