Thiophosgene → Methyl 3-bromo-4-{[(4-tert-butylcyclohexyl)(5-methoxy-1-methyl-1H-benz-imidazol-2-yl)amino]methyl}benzoate

Participants

Reaction Steps

To a solution of the title compound from Example 224 Step C (0.5 mmol, 191 mg) and DIEA (0.6 mmol, 104 μL) in 2 mL of DCM was added thiophosgene (0.5 mmol, 38 μL) (exothermic). After 15 min, the title compound from Example 14 Step B (0.6 mmol, 91 mg) was added to the reaction, followed by DIEA (0.6 mmol, 104 μL). The reaction mixture was allowed to stand at ambient temperature for 1 h, then Hg(O2CCF3)2 (0.6 mmol, 256 mg) was added (exothermic), affording a pinkish precipitate. After 30 min the solution was poured into saturated NaHCO3 containing Na2S, and the slurry was filtered through celite. The filter cake was washed with DCM. The organic layer of the filtrate and washings 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 brown residue. Purification by flash chromatography on silica eluting with 20% EtOAc/hexanes afforded the product as a slightly green foam. MS (ESI): m/z 542 (M+H), 544. HPLC A: 2.67 min.

Provenance & Evidence