Potassium Carbonate → 3-(N-(4-carboxybenzyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-N,N,N-trimethylpropan-1-aminium chloride

Participants

Reaction Steps

To a solution of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorphenylsulfonamido)-N,N,N-trimethylpropan-1-aminium chloride (96 mg, 0.13 mmol) in DMF (2 mL) was added K2CO3 (80 mg, 0.58 mmol) and methyl-(4-bromomethyl)-benzoate (40 mg, 0.18 mmol) at 25° C. and the resulting suspension was stirred for 24 h. The reaction mixture was quenched into water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and concentrated to a colorless oil. The oil was reconstituted in THF (6 mL) and added to a solution of LiOH.H2O (420 mg) in water (10 mL) at 25° C. After 30 min the reaction was concentrated and adjusted to pH 1 with conc HCl. The aqueous layer was extracted with DCM, and combined extracts were dried (MgSO4) and concentrated to furnish the title product (104 mg, 95%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J=8.2 Hz, 2H), 7.62 (d, J=6.4 Hz, 2H), 7.48 (d, J=8.2 Hz, 2H), 7.25 (d, J=8.3 Hz, 1H), 7.18 (s, 1H), 7.01 (t, J=8.7 Hz, 2H), 6.61 (dd, J=8.8, 4.9 Hz, 2H), 6.55 (d, J=1.8 Hz, 1H), 6.50 (dd, J=8.3, 1.9 Hz, 1H), 4.51 (s, 2H), 4.02 (s, 2H), 3.68 (s, 3H), 3.28-3.14 (m, 2H), 3.14-3.04 (m, 2H), 2.92 (s, 9H), 1.67 (d, J=8.3 Hz, 2H), 1.47 (s, 6H); MS (EI) m/z 815 (MH+).

Provenance & Evidence