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

HRID 1624841Notes

Reaction equation

HRID 1624841 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1.[NH:29]1[CH:33]=[CH:32][CH:31]=[N:30]1.OC1C=CC=CC=1C=NO.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:29]2[CH:33]=[CH:32][CH:31]=[N:30]2)=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 7200Salicylaldehyde oximeHCID 10796Cesium carbonateHCID 580722081-(2-Fluoro-5-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 580722871-[2-Fluoro-5-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-(2-fluoro-5-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (244 mg, 0.5 mmol), pyrazole (34.0 mg, 0.5 mmol), 2-hydroxybenzaldehyde oxime (27.4 mg, 0.2 mmol), Cu2O (7.2 mg, 0.05 mmol) and Cs2CO3 (326 mg, 1.0 mmol) in acetonitrile (1 mL) was heated to reflux for 14 h under Ar. The mixture was diluted with saturated NaHCO3 aqueous solution, extracted with AcOEt, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and on silica gel (hexane/AcOEt=50/50 to 0/100) and recrystallized with AcOEt/hexane to yield the title compound (8.3 mg, 4% yield) as a white solid: mp 186-187° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.78 (3H, s), 6.59-6.66 (1H, m), 6.95 (1H, d, J=1.9 Hz), 7.17-7.27 (1H, m), 7.30-7.42 (4H, m); 7.56-7.67 (1H, m), 7.76-7.90 (3H, m), 7.93-8.02 (1H, m), 8.47 (1H, d, J=2.6 Hz), 8.59 (1H, d, J=1.9 Hz). Anal. Calcd for C23H17FN6O2: C, 64.48; H, 4.00; N, 19.62. Found: C, 64.21; H, 4.08; N, 19.42.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 14 h under Ar
  3. extractionextracted with AcOEt
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and on silica gel (hexane/AcOEt=50/50 to 0/100)
  8. customrecrystallized with AcOEt/hexane

Sources & evidence

ORD record
ord-d7c886a6935742e680a85d48e5d300b2
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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