1,2-Dichloroethane → diethyl ether (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(2-(6-morpholino-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide

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Reaction Steps

To a solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.200 g, 0.476 mmol) in DCM (15 ml), DMAP (0.070 g, 0.571 mmol), EDC (0.274 g, 1.428 mmol) and 2-(6-morpholino-2,3-dioxoindolin-1-yl)acetic acid (0.166 g, 0.571 mmol) were added in one portion at room temperature, and the resulting solution was stirred overnight. The solvent was removed under vacuum and the crude was purified by silica gel flash chromatography (DCM:MeOH=98:2) to afford a red solid. After trituration with diethyl ether (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(2-(6-morpholino-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide was obtained (0.145 mg, 0.209 mmol, 44% yield). MS/ESI+ 692.31 [MH]+; [αD]=+227.4, c=0.25, MeOH; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.33 (s, 2H), 7.44 (d, 1H), 7.17 (d, 1H), 7.04 (d, 1H), 6.94 (dd, 1H), 7.08 (t, 1H), 6.59 (dd, 1H), 6.48 (d, 1H), 6.01 (dd, 1H), 4.56 (s, 2H), 3.90 (d, 2H), 3.63-3.80 (m, 4H), 3.43-3.55 (m, 4H), 3.37 (dd, 1H), 3.18 (dd, 1H), 1.13-1.35 (m, 1H), 0.50-0.66 (m, 2H), 0.23-0.48 (m, 2H)

Provenance & Evidence