1,2-Dichloroethane → HCID 86681708, compound

Participants

Reaction Steps

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (200 mg, 0.476 mmol), DMAP (116 mg, 0.952 mmol), and EDC (182 mg, 0.952 mmol) in DCM (10 ml), 2-(1,3-dioxo-5-(N-(thiophen-2-ylmethyl)methylsulfonamido)isoindolin-2-yl)acetic acid (225 mg, 0.571 mmol) was added portion wise, and the resulting mixture was stirred at room temperature for 18 hours. The solvent was evaporated, and the crude was purified by flash chromatography on silica gel (DCM/MeOH 10/0.5). The resulting product was triturated with iPr2O affording after filtration 227 mg of crude desired product. A further purification by flash chromatography on silica gel (DCM/acetone 8/1) was performed to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-5-(N-(thiophen-2-ylmethyl)methylsulfonamido)isoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (155 mg, 0.195 mmol, 40.9% yield, MS/ESI+ 796.02 [MH]+, [αD]=−30.31, c=0.415, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (s, 2H), 7.96 (d, 1H), 7.91 (d, 1H), 7.86 (dd, 1H), 7.40 (dd, 1H), 7.19 (d, 1H), 7.08 (d, 1H), 6.92-6.99 (m, 1H), 7.08 (t, 1H), 6.86 (d, 1H), 6.84 (d, 1H), 6.00 (dd, 1H), 5.25 (s, 2H), 4.39 (s, 2H), 3.81-4.09 (m, 2H), 3.37 (dd, 1H), 3.21 (s, 3H), 3.21 (dd, 1H), 1.17-1.37 (m, 1H), 0.50-0.69 (m, 2H), 0.21-0.46 (m, 2H)

Provenance & Evidence