反应详情

To a solution of 2,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylate (100 mg, 0.217 mmol; prepared according to Example 26) in dichloromethane (1 mL) was added (S)-3-aminopiperidin-2-one (prepared according to Example 3; 521 mg, 4.56 mmol), and the reaction mixture was allowed to stir overnight at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting with 50% acetone/hexanes to yield (S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopiperidin-3-yl)-1H-indazole-6-carboxamide (Ik) (1.00 g, 99%). Mass spec: 461 (M+1). 1H NMR (CDCl3) δ 8.53 (s, 1H), 8.40 (s, 1H), 7.90 (s, 1H), 7.15 (m, 1H), 7.03 (s, 1H), 6.99 (m, 1H), 6.90 (m, 1H), 6.09 (br, 1H), 4.56 (d, 1H), 4.53 (m, 1H), 3.36 (m, 2H), 2.70 (m, 1H), 1.97 (m, 1H), 1.66 (m, 1H), 1.39 (d, 3H), 1.38 (d, 3H).

1. washwashed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and saturated sodium chloride
2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified by column chromatography on silica gel
6. washeluting with 50% acetone/hexanes