反应详情

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.229 g, 0.544 mmol), 2-(5-(methylsulfonamidomethyl)-1,3-dioxoisoindolin-2-yl)acetic acid (0.170 g, 0.544 mmol), EDC (0.313 g, 1.633 mmol) and DMAP (0.133 g, 1.089 mmol) were dissolved in DCM (20 ml), and the solution was stirred at room temperature for 20 hours. The mixture was diluted with DCM and washed with 0.5N HCl, aqueous 5% NaHCO3 and brine. The organic phase was dried over sodium sulfate, and the solvent removed under vacuum. The crude was purified by preparative HPLC (Method 1) to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(methylsulfonamido methyl)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (0.120 g, 0.168 mmol, 30.9% yield, MS/ESI+ 714.06 [MH]+, [aD]=−27.89, c=0.9, DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.88-7.94 (m, 2H), 7.85 (dd, 1H), 7.77 (t, 1H), 7.19 (d, 1H), 7.08 (s, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.01 (dd, 1H), 4.42 (s, 2H), 4.23-4.56 (m, 2H), 3.83-4.00 (m, 2H), 3.39 (dd, 1H), 3.22 (dd, 1H), 2.95 (s, 3H), 1.10-1.34 (m, 1H), 0.49-0.67 (m, 2H), 0.30-0.46 (m, 2H)

1. washwashed with 0.5N HCl, aqueous 5% NaHCO3 and brine
2. dry with materialThe organic phase was dried over sodium sulfate
3. customthe solvent removed under vacuum
4. customThe crude was purified by preparative HPLC (Method 1)