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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 1407325
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HRID 1407325 반응식
[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
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참가 물질

6

반응물 3

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

생성물 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)-one수율 46%

시약·촉매·용매 2

HCID 313Hydrochloric Acid
용매
HCID 78373Dimethylformamide dimethyl acetal용매

실험 절차

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;

후처리

  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

출처 및 근거

ORD 기록
ord-399b7bb2e59146088bcf3eb721209d2f
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08916566B2

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