反应详情

5-(2,4-Difluorophenoxy)-1-(2-hydroxy-2-methylpropyl)-1H-indazole-6-carboxylic acid (200 mg, 0.552 mmol) was dissolved in N,N-dimethylformamide (2 mL). To his was added (S)-3-aminopyrrolidin-2-one (4a) (111 mg, 1.10 mmol), 4-(dimethylamino)pyridine (6.7 mg, 0.055 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (116 mg, 0.607 mmol) successively, and the reaction mixture was allowed to stir at ambient temperature for 16 hours. The reaction mixture was partitioned between water and ethyl acetate, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on a silica gel column, eluting with 100% acetone to yield pure (S)-5-(2,4-difluorophenoxy)-1-(2-hydroxy-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide (Ij) (83 mg, 34%). Mass spec: 445 (M+1). 1H NMR (CDCl3) δ 8.39 (s, 1H), 8.26 (brd, 1H), 7.93 (s, 1H), 7.18 (m, 1H), 7.04 (s, 1H), 7.02 (m, 1H), 6.92 (m, 1H), 6.04 (br, 1H), 4.59 (ddd, 1H), 4.37 (s, 2H), 3.64 (brs, 1H), 3.45 (m, 2H), 2.87 (m, 1H), 2.09 (m, 1H), 1.21 (s, 3H), 1.12 (s, 3H).

1. customThe reaction mixture was partitioned between water and ethyl acetate
2. extractionthe aqueous layer was extracted twice with ethyl acetate
3. dry with materialThe combined organic layers were 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 100% acetone