Triethylamine → methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate

Participants

Reaction Steps

A mixture of 4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoic acid (0.85 mmol from previous step) and β-alanine methyl ester hydrochloride (139 mg, 1.0 mmol) in DCM (10 mL) was treated with Et3N (0.36 mL, 2.6 mmol) and HATU (390 mg, 1.0 mmol) at ambient temperature. After stirring for 16 h at ambient temperature the reaction mixture was quenched by the addition of H2O, 1N HCl, and DCM. The aqueous layer was extracted with DCM. The combined extracts were washed with satd NaHCO3, dried over Na2SO4 and concentrated under reduced pressure to afford crude product. This material was purified by flash chromatography (silica gel, EtOAc/Hex, 0:100 to 100:0) to give methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate as a clear syrup, that was carried on to the next step directly. 1H NMR (400 MHz, CDCl3) δ 7.31-7.23 (m, 2H), 7.19 (s, 1H), 7.09 (d, J=2.2 Hz, 1H), 6.99 (t, J=5.5 Hz, 1H), 6.88 (ddd, J=10.7, 9.6, 5.4 Hz, 2H), 6.26 (ddd, J=8.5, 3.8, 2.5 Hz, 1H), 5.91 (dd, J=7.5, 2.4 Hz, 1H), 4.16-4.08 (m, 2H), 3.76-3.66 (m, 5H), 3.50 (s, 3H), 2.66 (t, J=5.9 Hz, 2H), 1.89 (s, 1H), 1.54 (s, 3H), 1.47 (s, 3H); MS (EI) m/z 666 (MH+).

Provenance & Evidence