(3S)-3-aminopyrrolidin-2-one → (S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide

Participants

Reaction Steps

To a solution of 2,5-dioxopyrrolidin-1-yl 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylate (700 mg, 1.58 mmol) in dichloromethane (5 mL) was added (S)-3-aminopyrrolidin-2-one (prepared according to Example 2, 205 mg, 2.05 mmol) and the reaction 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 a silica gel column, eluting with a gradient of 25-100% acetone/hexanes to yield (S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide (Ia) (520 mg, 77%). Mass spec: 429 (M+1). 1H NMR (CDCl3) δ 8.37 (s, 1H), 8.26 (d, 1H), 7.87 (s, 1H), 7.15 (m, 1H), 7.03 (s, 1H), 7.00 (m, 1H), 6.91 (m, 1H), 6.03 (br, 1H), 4.59 (ddd, 1H), 4.22 (d, 2H), 3.46 (m, 2H), 2.87 (m, 1H), 2.36 (m, 1H), 2.10 (m, 1H), 0.92 (d, 6H).

Provenance & Evidence