1,2-Dichloroethane → HCID 86681668, compound

Participants

Reaction Steps

A mixture of 2-(5-(methylsulfonamido)indolin-1-yl)acetic acid (0.154 g, 0.571 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.200 g, 0.476 mmol), EDC (0.128 g, 0.666 mmol) and DMAP (0.116 g, 0.952 mmol) in dry DCM (10 ml) was stirred at room temperature for 2.5 hours. Additional 2-(5-(methylsulfonamido)indolin-1-yl)acetic acid (0.072 g, 0.267 mmol) was added, and the mixture was stirred overnight at room temperature. The solvent was removed and the crude was purified by flash chromatography on silica gel column (DCM:MeOH=98:2). A further purification by preparative HPLC (Method 1) under neutral conditions was required to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(methylsulfonamido)indolin-1-yl)acetoxy)ethyl)-pyridine 1-oxide (0.0817 g, 0.121 mmol, 26% yield). MS/ESI+ 672.05 [MH]+; [αD]=+10.81, c=0.518; DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.84 (br. s., 1H), 8.55 (s, 2H), 7.17 (d, 1H), 7.08 (d, 1H), 6.94 (dd, 1H), 6.92 (d, 1H), 7.06 (t, 1H), 6.81 (dd, 1H), 6.22 (d, 1H), 6.03 (dd, 1H), 4.10 (d, 1H), 3.90 (d, 2H), 3.92 (d, 1H), 3.43 (dd, 1H), 3.32-3.39 (m, 2H), 3.22 (dd, 1H), 2.89 (t, 2H), 2.83 (s, 3H), 1.08-1.31 (m, 1H), 0.49-0.68 (m, 2H), 0.18-0.46 (m, 2H).

Provenance & Evidence