Phenylhydrazine → 1-(2,5-Difluoro-4-morpholin-4-ylphenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624852Notes

Reaction equation

HRID 1624852 reaction equation
[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]([F:19])[C:16]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:15][C:14]=2[F:26])[N:5]=1)(=O)[CH3:2].[CH3:27]OC(OC)N(C)C.[C:35]1([NH:41][NH2:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CCOC(C)=O>[F:26][C:14]1[CH:15]=[C:16]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:17]([F:19])=[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:41]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:42]=[CH:27][CH:2]=2)=[N:5]1

Participants

5

Reactant 3

HCID 7516PhenylhydrazineHCID 78373Dimethylformamide dimethyl acetalHCID 58072369HCID 58072369, compound

Product 1

HCID 580725101-(2,5-Difluoro-4-morpholin-4-ylphenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 36%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-acetyl-1-(2,5-difluoro-4-morpholin-4-ylphenyl)-5-methoxypyridazin-4(1H)-one (340 mg, 0.93 mmol) and N,N-dimethylformamide dimethyl acetal (3.4 mL) was stirred at 120° C. for 2.5 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in AcOH (3.4 mL) and phenylhydrazine (0.18 mL, 1.9 mmol) was added. This mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with AcOEt, and washed with saturated NaHCO3 aqueous solution and brine. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The residue was recrystallized from AcOEt/MeOH to give the title compound (156 mg, 36% yield) as a pale orange solid: mp 211-212° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 2.99-3.15 (4H, m), 3.60-3.88 (7H, m), 6.85 (1H, dd, J=12.8, 7.2 Hz), 6.99 (1H, d, J=2.3 Hz), 7.09 (1H, dd, J=12.8, 7.6 Hz), 7.24-7.50 (5H, m), 7.79 (1H, d, J=1.9 Hz), 8.43 (1H, d, J=2.3 Hz). LC-MS (ESI) m/z 466 [M+H]+. Anal. Calcd for C24H21F2N5O3.0.5H2O: C, 60.75; H, 4.67; N, 14.76. Found: C, 60.98; H, 4.71; N, 14.63.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in AcOH (3.4 mL)
  4. stirringThis mixture was stirred at room temperature for 1 h
  5. washwashed with saturated NaHCO3 aqueous solution and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was recrystallized from AcOEt/MeOH

Sources & evidence

ORD record
ord-91754a9cf2d64e2099e22985fe94e434
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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