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

HRID 884766

Reaction equation

HRID 884766 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
67.5 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-bd8f3ebe1cb244c8b78d8dfc5fa37725
Source dataset
uspto-grants-2012_08
Patent number
US08242117B2

Linked notes

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