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

HRID 251330

Reaktionsgleichung

Reaktionsgleichung von HRID 251330
[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

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
67.5 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-c82751709aef41d883ebe0318ddc908b
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863314B2

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