Ethyl Acetate → 3-[5-amino-4-(3-iodo-benzoyl)-pyrazol-1-yl]-N-methoxy-4-methyl-benzamide

HRID 884766

反応式

HRID 884766 の反応式
[NH:1]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[CH3:14])[C:6]([NH:8][O:9][CH3:10])=[O:7])[NH2:2].[I:15][C:16]1[CH:17]=[C:18]([CH:32]=[CH:33][CH:34]=1)[C:19]([C:21](=[CH:24]NC1C=CC=CC=1)[C:22]#[N:23])=[O:20].CCOC(C)=O>CCO>[NH2:23][C:22]1[N:1]([C:3]2[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=2[CH3:14])[C:6]([NH:8][O:9][CH3:10])=[O:7])[N:2]=[CH:24][C:21]=1[C:19](=[O:20])[C:18]1[CH:32]=[CH:33][CH:34]=[C:16]([I:15])[CH:17]=1

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 116153463-hydrazino-N-methoxy-4-methyl-benzamide2 回HCID 670242742-(3-Iodobenzoyl)-3-phenylaminoacrylonitrile

生成物 1

HCID 117848203-[5-amino-4-(3-iodo-benzoyl)-pyrazol-1-yl]-N-methoxy-4-methyl-benzamide収率 55%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
67.5 °C

実験手順

To a stirred solution 3-hydrazino-N-methoxy-4-methyl-benzamide 2 (116 mg, estimated 0.14 mmol) in EtOH (10 ml) was added 2-(3-iodo-benzoyl)-3-phenylamino-acrylonitrile 3 (59 mg, 0.14 mmol, preparation: International Patent Application Publication No. WO 02/57101 A1, pg. 84) and mixture was heated (bath T=65-70° C.) for 4 hr, when additional 3-hydrazino-N-methoxy-4-methyl-benzamide 2 (80 mg, 0.11 mmol) was added and the mixture was heated at the same temperature for 27 hr. It was cooled to room temperature, concentrated and redissolved in EtOAc before it was washed with water and brine, dried over Na2SO4, concentrated to give a crude semisolid. The mixture was then purified by flash chromatography, eluting with 1:1 EtOAc/hexanes to remove impurities then 100% EtOAc give 3-[5-amino-4-(3-iodo-benzoyl)-pyrazol-1-yl]-N-methoxy-4-methyl-benzamide 4 as an off-white solid (38 mg, 0.08 mmol, 55%). HPLC (6 minute gradient) tR 3.49 min; MS m/z 476.96 [M+H]+; 1H NMR (CD3OD, 300 MHz) δ 8.10 (s, 1 H), 7.95 (d, J=8.0, 1 H), 7.88 (d, J=8.0, 1 H), 7.82 (m, 2 H), 7.78 (s, 1 H), 7.58 (d, J=8.0, 1 H), 7.33 (t, J=7.8, 1 H), 5.02 (s. 3 H), 2.33 (s, 3 H) ppm; 13C NMR (DMSO-d6, 125 MHz.) δ 189.3, 154.3, 143.5, 143.3, 142.0, 138.3, 137.4, 133.5, 132.9, 132.0, 130.4, 128.8, 128.4, 104.8, 95.4, 64.8, 18.2 ppm.

後処理

  1. custom59 mg, 0.14 mmol, preparation
  2. temperaturethe mixture was heated at the same temperature for 27 hr
  3. temperatureIt was cooled to room temperature
  4. concentrationconcentrated
  5. dissolutionredissolved in EtOAc before it
  6. washwas washed with water and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto give a crude semisolid
  10. customThe mixture was then purified by flash chromatography
  11. washeluting with 1:1 EtOAc/hexanes
  12. customto remove impurities

出典と根拠

ORDレコード
ord-bd8f3ebe1cb244c8b78d8dfc5fa37725
出典データセット
uspto-grants-2012_08
特許番号
US08242117B2

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