Ethanol → 2-(2-fluorophenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 449941Notes

Reaction equation

HRID 449941 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16](=S)[C:15]([C:24](OCC)=[O:25])=[N:14]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.C(O)C.[F:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[NH:39][NH2:40].C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(Cl)(Cl)Cl>[F:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[N:39]1[C:24](=[O:25])[C:15]2=[N:14][N:13]([CH2:12][C:9]3[CH:10]=[CH:11][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:7][CH:8]=3)[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]2=[N:40]1

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 4238442-Fluorophenylhydrazine hydrochlorideHCID 86659984ethyl 1-[4-(1H-pyrazol-1-yl)benzyl]-4-thioxo-1,4-dihydrocinnoline-3-carboxylate

Product 1

HCID 468964002-(2-fluorophenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ethyl 1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-4-thioxo-1,4-dihydrocinnoline-3-carboxylate (160 mg, 0.410 mmol) was dissolved in 1,2-dimethoxyethane (2 mL) and absolute ethanol (1 mL). 2-Fluorophenylhydrazine (114 mg, 0.902 mmol, 2.2 equiv) and potassium carbonate (170 mg, 1.23 mmol, 3.0 equiv) were added. The mixture was stirred vigorously for 15 minutes at ambient temperature and then placed into an oil bath preheated to 98° C. for 7 hours. The mixture was cooled ambient temperature, diluted with chloroform and washed once with water. The aqueous layer was extracted once with chloroform and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 99:1; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.32 (1H, d, J=7.8 Hz), 7.90 (1H, s), 7.71-7.61 (4H, m), 7.60-7.52 (3H, m), 7.43-7.37 (3H, m), 7.31-7.26 (2H, m), 6.47 (1H, s), 5.88 (2H, s) ppm; high resolution mass spectrometry (ES+) m/z 437.1517 [(M+H)+; calculated for C25H18FN6O: 437.1521].

Workup

  1. customplaced into an oil bath
  2. waitpreheated to 98° C. for 7 hours
  3. temperatureThe mixture was cooled ambient temperature
  4. washwashed once with water
  5. extractionThe aqueous layer was extracted once with chloroform
  6. dry with materialthe combined organic extracts were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel gradient chromatography (100:0 to 99:1; chloroform:methanol)

Sources & evidence

ORD record
ord-adf0e6bb773340f5ae95e19ef9efda11
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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