Methanesulfonyl chloride → 3-(3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)phenylsulfonamido)propyl methanesulfonate

Participants

Reaction Steps

To a solution of 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(3-hydroxypropyl)benzenesulfonamide (910 mg, 1.42 mmol) and diisopropylethylamine (0.74 mL, 0.74 mmol) in DCM (6 mL) was added methanesulfonyl chloride (0.13 mL, 1.706 mmol) at −10° C. After the reaction was slowly warmed to ambient temperature over 30 min, it was extracted with DCM (10 mL). The combined extracts were washed with water (10 mL), dried over MgSO4 and evaporated in vacuo. The residue was purified by column chromatography (Hex:EA=1:2) to give 3-(3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)phenylsulfonamido)propyl methanesulfonate (0.80 g, 78% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.63 (s, 1H), 7.39 (dd, J=8.27, 1.73 Hz, 1H), 7.27 (d, J=2.32 Hz, 2H), 6.89 (dd, J=10.97, 8.54 Hz, 1H), 6.84-6.74 (m, 2H), 6.58 (dd, J=8.09, 2.16 Hz, 1H), 6.53-6.45 (m, 1H), 6.41-6.33 (m, 2H), 5.26 (s, 1H), 4.42-4.29 (m, 2H), 4.23-4.08 (m, 3H), 3.78 (d, J=2.18 Hz, 4H), 3.21-3.10 (m, 2H), 3.10-2.99 (m, 4H), 2.00 (dd, J=11.78, 6.04 Hz, 2H), 1.65 (s, 7H).

Provenance & Evidence