反应详情

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (100 mg, 0.238 mmol) was placed in a 50 ml round bottom flask and dissolved in DMF (3 ml); EDC (45.6 mg, 0.238 mmol) was added to it followed by DMAP (29.1 mg, 0.238 mmol) and 2-(4-nitro-1,3-dioxoisoindolin-2-yl)acetic acid (90 mg, 0.357 mmol). The reaction was stirred at RT for 6 hours. The reaction was quenched by adding 30 ml of HCl/H2O (1M) and extracted with EtOAc (30 ml). The organic phase (EtOAc) was extracted with HCl/H2O 1M (30 ml; ×3) and subsequently with K2CO3/H2O (20 ml; ×3). The resulting organic extract was dried over Na2SO4, filtered and the solvent removed under reduced pressure to yield 120 mg of title compound (77% yield). 1H NMR (400 MHz, acetone) δ. ppm 8.35 (d, J=7.50 Hz, 1H), 8.24-8.30 (m, 1H), 8.16-8.24 (m, 3H), 7.16-7.25 (m, 2H), 7.05 (dd, J=8.16, 1.98 Hz, 1H), 6.94 (t, 1H, CHF2), 6.14 (dd, J=9.48, 4.63 Hz, 1H), 4.52 (s, 2H), 4.01 (dd, J=6.62, 3.97 Hz, 2H), 3.54 (dd, J=14.33, 9.48 Hz, 1H), 3.26-3.40 (m, 1H), 1.25-1.38 (m, 1H), 0.56-0.73 (m, 2H), 0.36-0.48 (m, 2H); MS/ESI+ 652.1 [MH]+

1. customThe reaction was quenched
2. additionby adding 30 ml of HCl/H2O (1M)
3. extractionextracted with EtOAc (30 ml)
4. extractionThe organic phase (EtOAc) was extracted with HCl/H2O 1M (30 ml; ×3) and subsequently with K2CO3/H2O (20 ml; ×3)
5. extractionThe resulting organic extract
6. dry with materialwas dried over Na2SO4
7. filtrationfiltered
8. customthe solvent removed under reduced pressure