反应详情

(S)-3-Amino-1-methylpyrrolidin-2-one hydrochloride (211 mg, 1.40 mmol) was dissolved in triethylamine (0.195 mL, 1.40 mmol) and dichloromethane (7 mL). To this, 2,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylate (prepared according to Example 16, Step A; 651 mg, 0.677 mmol) was added, and the reaction was allowed to stir at ambient temperature for 16 hours. The crude reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on a silica gel column, eluting with 25% acetone/hexanes to yield pure (S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(1-methyl-2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide (Id) (360 mg, 58%). Mass spec: 443 (M+1). 1H NMR (CDCl3) δ 8.36 (s, 1H), 8.29 (br, 1H), 7.18 (m, 1H), 7.01 (m, 2H), 6.92 (m, 1H), 4.56 (ddd, 1H), 4.22 (d, 2H), 3.42 (m, 2H), 2.93 (s, 3H), 2.82 (m, 1H), 2.37 (m, 1H), 1.99 (m, 1H), 0.92 (d, 6H).

1. customThe crude reaction mixture
2. washwashed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and brine
3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was purified by flash chromatography on a silica gel column
7. washeluting with 25% acetone/hexanes