L-2-aminohexano-6-lactam → (S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxoazepan-3-yl)-1H-indazole-6-carboxamide

HRID 912450

反応式

HRID 912450 の反応式
[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:16][C@H:17]1[CH2:21][CH2:20][NH:19][C:18]1=[O:22])=[O:15])[N:10]([CH2:23][CH:24]([CH3:26])[CH3:25])[N:9]=[CH:8]2.N[C@H:33]1CCCCN[C:34]1=O>ClCCl.C(OCC)(=O)C>[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:16][C@H:17]1[CH2:34][CH2:33][CH2:21][CH2:20][NH:19][C:18]1=[O:22])=[O:15])[N:10]([CH2:23][CH:24]([CH3:25])[CH3:26])[N:9]=[CH:8]2

参加物

5

反応物 2

HCID 440599L-2-aminohexano-6-lactamHCID 17751071(S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide

生成物 1

HCID 24864922(S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxoazepan-3-yl)-1H-indazole-6-carboxamide収率 94%

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-isobutyl-1H-indazole-6-carboxylate (Example 16; 300 mg, 0.677 mmol) in dichloromethane (3 mL) was added (S)-3-aminoazepan-2-one (prepared according to Example 4; 173 mg, 1.35 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 80% ethyl acetate/hexanes to yield (S)-5-(2,4-difluorophenoxy)-1-isobutyl-N-(2-oxoazepan-3-yl)-1H-indazole-6-carboxamide (Ic) (290 mg, 94%). Mass spec: 457 (M+1). 1H NMR (CDCl3) δ 9.11 (br, 1H), 8.33 (s, 1H), 7.86 (s, 1H), 7.16 (m, 1H), 7.04 (s, 1H), 7.00 (m, 1H), 6.89 (m, 1H), 6.14 (br, 1H), 4.78 (ddd, 1H), 4.22 (d, 2H), 3.34 (m, 1H), 3.24 (m, 1H), 2.35 (m, 1H), 2.26 (m, 1H), 2.07 (m, 1H), 1.89 (m, 2H), 1.57 (m, 1H), 1.42 (m, 1H), 0.93 (d, 6H).

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 80% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-8fb30d07a7d64311ae1960a2a682b65d
出典データセット
uspto-grants-2011_09
特許番号
US08026233B2

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