Acetic Acid → 1-(3-Bromo-2-fluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1407304ノート

反応式

HRID 1407304 の反応式
[C:1]([C:4]1[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[C:14]=2[F:20])[N:5]=1)(=O)[CH3:2].[CH3:21]C(O)=O.[C:25]1([NH:31][NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>COC(OC)N(C)C.Cl>[Br:19][C:15]1[C:14]([F:20])=[C:13]([N:6]2[CH:7]=[C:8]([O:11][CH3:12])[C:9](=[O:10])[C:4]([C:1]3[N:31]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:32]=[CH:21][CH:2]=3)=[N:5]2)[CH:18]=[CH:17][CH:16]=1

参加物

6

反応物 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 594362583-Acetyl-1-(3-bromo-2-fluorophenyl)-5-methoxypyridazin-4(1H)-one

生成物 1

HCID 580723441-(3-Bromo-2-fluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one収率 59%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 78373Dimethylformamide dimethyl acetal溶媒

実験手順

A mixture of 3-acetyl-1-(3-bromo-2-fluorophenyl)-5-methoxypyridazin-4(1H)-one (2.98 g, 8.74 mmol) in N,N-dimethylformamide dimethyl acetal (30 mL) was heated to reflux for 3.5 h. The mixture was concentrated in vacuo. To the residue were added AcOH (30 mL) and phenylhydrazine (1.72 mL, 17.5 mmol). The mixture was heated to reflux for 4 h. The mixture was diluted with 1 M HCl aqueous solution, extracted with AcOEt, washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and recrystallized with EtOH to yield the title compound (2.29 g, 59% yield) as a yellow solid: mp 186-191° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.77 (3H, s), 6.99 (1H, d, J=1.9 Hz), 7.08-7.15 (1H, m), 7.17-7.26 (1H, m), 7.28-7.47 (5H, m), 7.74-7.86 (2H, m), 8.55 (1H, d, J=2.3 Hz). Anal. Calcd for C20H14BrFN4O2: C, 54.44; H, 3.20; N, 12.70. Found: C, 54.70; H, 3.30; N, 12.82.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 3.5 h
  3. concentrationThe mixture was concentrated in vacuo
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 4 h
  6. extractionextracted with AcOEt
  7. washwashed with saturated NaHCO3 aqueous solution
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100)
  12. customrecrystallized with EtOH

出典と根拠

ORDレコード
ord-1abf3a6936664d7aaf12ad8c02be2a31
出典データセット
uspto-grants-2014_12
特許番号
US08916566B2

反応ノート

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