反应详情

A mixture of 2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-2-oxoindolin-1-yl)acetic acid hydrochloride (0.105 g, 0.242 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.092 g, 0.220 mmol), EDC (0.127 g, 0.660 mmol), and DMAP (0.054 g, 0.440 mmol) in DCM (15 ml) was stirred at room temperature for 24 hours. The mixture was diluted with DCM and washed with aqueous sat. NH4Cl and aqueous 5% NaHCO3; the organic phase was dried over sodium sulfate and the solvent was removed. The crude was purified by flash chromatography on silica gel column (DCM:MeOH=99:1 to 96:4) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-morpholinoethyl)-methylsulfonamido)-2-oxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.070 g, 0.088 mmol, 39.8% yield, MS/ESI+ 799.46 [MH]+, [αD]=−40.88, c=0.25, MeOH). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.32 (s, 1H), 7.26 (dd, 1H), 7.19 (d, 1H), 7.11 (d, 1H), 6.97 (dd, 1H), 6.83 (d, 1H), 7.07 (t, 1H), 6.03 (dd, 1H), 4.61 (d, 1H), 4.50 (d, 1H), 3.95 (d, 2H), 3.70 (t, 2H), 3.67 (s, 2H), 3.48-3.57 (m, 4H), 3.39 (dd, 1H), 3.22 (dd, 1H), 3.07 (s, 3H), 2.30-2.43 (m, 6H), 1.14-1.34 (m, 1H), 0.50-0.69 (m, 2H), 0.25-0.46 (m, 2H).

1. washwashed with aqueous sat. NH4Cl and aqueous 5% NaHCO3
2. dry with materialthe organic phase was dried over sodium sulfate
3. customthe solvent was removed
4. customThe crude was purified by flash chromatography on silica gel column (DCM:MeOH=99:1 to 96:4)