Methyl malonyl chloride → 3-[2-(4-Benzyloxyphenyl)-1-cyclohexyl-1H-benzimidazole-5-sulfonylamino]-3-oxo-propionic acid methyl ester

Participants

Reaction Steps

A solution of intermediate 69 (0.046 g, 0.1 mmol) in dichloromethane (0.700 mL) was cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran) (0.10 ml, 0.10 mmol) was added and the mixture was stirred for 1 hr. Methyl-3-chloro-3-oxo-propionate (0.011 ml, 0.10 mmol was added. The reaction mixture was stirred at rt overnight. The reaction mixture was concentrated and the residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford the product (0.005 g, 7%). 1H NMR (CDCl3) δ 8.60 (s, 1H), 8.16 (d, 1H, J=8.8 Hz), 7.85 (d, 1H, J=8.8 Hz), 7.64 (d, 2H, J=8.8 Hz), 7.50-7.38 (m, 5H), 7.21 (d, 2H, J=8.8 Hz), 5.18 (s, 2H), 4.49 (m, 1H), 3.70 (s, 3H), 3.35 (s, 2H), 2.30 (br m, 2H), 2.02 (br m, 4H), 1.82 (br m, 1H), 1.35 (br m, 3H); ESI-MS m/e 562.18(M+1); HPLC purity (UV) 99%.

Provenance & Evidence