Reaction Steps
A mixture of 2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-2,3-dioxoindolin-1-yl)acetic acid 2,2,2-trifluoroacetic acid salt (0.319 g, 0.607 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.170 g, 0.405 mmol), EDC (0.233 g, 1.214 mmol), and DMAP (0.099 g, 0.809 mmol) in DCM (25 ml) was stirred at room temperature for 3 days. The mixture was diluted with DCM and washed with aqueous 5% NaHCO3 and with sat. NH4Cl; the organic phase was dried over sodium sulfate, and the solvent was removed. The crude was purified by flash chromatography on silica gel cartridge (DCM:MeOH=99:1 to 95:5). An additional purification by chromatography on silica gel column (DCM:MeOH=98:2 to 97:3) was performed to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.113 g, 0.139 mmol, 34.3% yield, MS/ESI+ 813.19 [MH]+, [αD]=−26.83, c=0.24, MeOH). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.43 (s, 2H), 7.69 (d, 1H), 7.68 (dd, 1H), 7.19 (d, 1H), 7.10 (d, 1H), 7.09 (d, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.04 (dd, 1H), 4.69 (d, 1H), 4.58 (d, 1H), 3.93 (d, 2H), 3.74 (t, 2H), 3.46-3.55 (m, 4H), 3.40 (dd, 1H), 3.23 (dd, 1H), 3.08 (s, 3H), 2.37 (t, 2H), 2.28-2.34 (m, 4H), 1.08-1.36 (m, 1H), 0.47-0.66 (m, 2H), 0.27-0.49 (m, 2H).
