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Acetic Acid → 1-[2-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624805
ノート
印刷プレビュー

反応式

HRID 1624805 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]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[CH:16]=[CH:15][C:14]=2[F:25])[N:5]=1)(=O)[CH3:2].[CH3:26]C(O)=O.[C:30]1([NH:36][NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>COC(OC)N(C)C.Cl>[F:25][C:14]1[CH:15]=[CH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:18][C:13]=1[N:6]1[CH:7]=[C:8]([O:11][CH3:12])[C:9](=[O:10])[C:4]([C:1]2[N:36]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:37]=[CH:26][CH:2]=2)=[N:5]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 594362133-Acetyl-1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one

生成物 1

HCID 580724501-[2-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one収率 46%

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-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one (200 mg, 0.585 mmol) in N,N-dimethylformamide dimethyl acetal (2.0 mL) was heated to reflux for 3 h. The mixture was concentrated in vacuo. To the residue were added AcOH (2.0 mL) and phenylhydrazine (0.115 mL, 1.17 mmol). The mixture was heated to reflux for 3 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 by HPLC and recrystallized with EtOH/hexane to yield the title compound (118 mg, 46% yield) as a white solid: mp 93-102° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.78 (3H, s), 3.89 (3H, s), 6.91 (1H, d, J=1.9 Hz), 7.20-7.52 (7H, m), 7.63-7.71 (1H, m), 7.78 (1H, d, J=1.9 Hz), 7.83 (1H, s), 8.10 (1H, s), 8.53 (1H, d, J=1.6 Hz). Anal. Calcd for C24H19FN6O2.1.3H2O: C, 61.88; H, 4.67; N, 18.04. Found: C, 61.63; H, 4.64; N, 18.09.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 3 h
  3. concentrationThe mixture was concentrated in vacuo
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 3 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) and by HPLC
  12. customrecrystallized with EtOH/hexane

出典と根拠

ORDレコード
ord-1df5f698703d41d29c72abf90b506368
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08778944B2

反応ノート

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