Triethylamine → (S)-5-(2,4-difluorophenoxy)-N-(1-(2-hydroxyethyl)-2-oxopiperidin-3-yl)-1-isobutyl-1H-indazole-6-carboxamide

(S)-3-Amino-1-(2-hydroxyethyl)piperidin-2-one hydrochloride (52 mg, 0.27 mmol) was dissolved in triethylamine (0.075 mL, 0.54 mmol) and N,N-dimethylformamide (1 mL). To this was added 2,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylate (prepared according to Example 16, Step A; 119 mg, 0.268 mmol), and the reaction mixture was allowed to stir at ambient temperature for 48 hours. The 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 50% acetone/hexanes to yield pure (S)-5-(2,4-difluorophenoxy)-N-(1-(2-hydroxyethyl)-2-oxopiperidin-3-yl)-1-isobutyl-1H-indazole-6-carboxamide (1 h) (104 mg, 80%). Mass spec: 487 (M+1). 1H NMR (CDCl3) δ 8.57 (brd, 1H), 8.32 (s, 1H), 7.87 (s, 1H), 7.14 (m, 1H), 7.03 (s, 1H), 7.00 (m, 1H), 6.89 (m, 1H), 4.47 (ddd, 1H), 4.22 (d, 2H), 3.82 (m, 2H), 3.68 (m, 1H), 3.47 (m, 3H), 2.90 (m, 1H), 2.62 (m, 1H), 2.36 (m, 1H), 2.00 (m, 2H), 1.74 (m, 1H), 0.93 (d, 6H).

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

ORDレコード

ord-32c9ada06453464b8dd0c0ccc5f7aff2

出典データセット

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08026233B2