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

HRID 912466

반응식

HRID 912466 반응식
O=C1CCC(=O)N1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:26]([O-:28])=O)=[C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])[CH:15]=2)[N:10]([CH2:29][C:30]([F:33])([CH3:32])[CH3:31])[N:9]=1.[NH2:34][C@H:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40]>ClCCl.C(OCC)(=O)C>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[C:26]([NH:34][C@H:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40])=[O:28])[N:10]([CH2:29][C:30]([F:33])([CH3:32])[CH3:31])[N:9]=[CH:8]2

참가 물질

5

반응물 2

HCID 12430456(3S)-3-aminopyrrolidin-2-oneHCID 866310522,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylate

생성물 1

HCID 24865103(S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide수율 1,032.3%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylate (prepared according to Example 26; 100 mg, 0.217 mmol) in dichloromethane (1 mL) was added (S)-3-aminopyrrolidin-2-one (4a) 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 a silica gel column, eluting with 50% acetone/hexanes to yield (S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide (Ik) (1.00 g, 99%). Mass spec: 447 (M+1). 1H NMR (CDCl3) δ 8.42 (s, 1H), 8.21 (br, 1H), 7.15 (m, 1H), 7.03 (s, 1H), 7.01 (m, 1H), 6.91 (m, 1H), 6.59 (br, 1H), 4.58 (m, 1H), 4.55 (d, 2H), 3.43 (m, 2H), 2.84 (m, 1H), 2.06 (m, 1H), 1.40 (d, 3H), 1.39 (d, 3H).

후처리

  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 a silica gel column
  6. washeluting with 50% acetone/hexanes

출처 및 근거

ORD 기록
ord-63863af0cc644b8ca06c3d955ebe43e7
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026233B2

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