1-Hydroxybenzotriazole → methyl 4-[1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxy phenylacetyl]-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate

Participants

Reaction Steps

A mixture of methyl 4-(4,4-difluoro-2-pyrrolidinylmethoxy)benzoate (229 mg, 0.845 mmol), 4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid (283 mg, 0.845 mmol), EDC.HCl (243 mg, 1.27 mmol), HOBt (cat.), DMAP (cat.), and DMF (10 ml) was stirred overnight. The mixture was diluted with EtOAc (300 ml). The solution was washed with brine (2×100 ml), dried over MgSO4, and concntrated in vacuo. The residue was chromatographed on silica gel with CHCl3-EtOAc (20:1 to 4:1) as eluent to give methyl 4-[1-[4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate (482 mg, 97%) as a colorless viscous solid. 1H-NMR (CDCl3) δ2.50-2.67 (m, 2 H), 3.54-4.71 (series of m, 13 H), 6.69 (d, J=1.5 Hz, 1 H), 6.76 (d, J=8.3 Hz, 1 H), 6.84 (d, J=8.8 Hz, 2 H), 6.98 (dt, J=7.8, 1.5 Hz, 1 H), 7.23-7.27 (m, 1 H), 7.33 (d, J=8.3 Hz, 1 H), 7.39 (m, 2 H), 7.94 (d, J=8.8 Hz, 2 H), 8.00 (d, J=8.3 Hz, 1 H), 8.19 (dd, J=8.3, 1.5 Hz, 1 H).

Provenance & Evidence