(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

反応式

HRID 912466 の反応式
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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-63863af0cc644b8ca06c3d955ebe43e7
出典データセット
uspto-grants-2011_09
特許番号
US08026233B2

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