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

HRID 912450

반응식

HRID 912450 반응식
[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

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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).

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 80% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-8fb30d07a7d64311ae1960a2a682b65d
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026233B2

연결된 노트

불러오는 중…