Phenylhydrazine → HCID 58072180, compound

HRID 1895384Notes

Reaction equation

HRID 1895384 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]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[C:15]([F:25])[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>>[F:26][C:14]1[C:15]([F:25])=[C:16]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[CH:17]=[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

4

Reactant 3

HCID 7516PhenylhydrazineHCID 78373Dimethylformamide dimethyl acetalHCID 58072486HCID 58072486, compound

Product 1

HCID 58072180HCID 58072180, compoundYield 55%

Conditions

Temperature
120 °C

Procedure

A mixture of 3-acetyl-1-(2,3-difluoro-4-morpholin-4-ylphenyl)-5-methoxypyridazin-4(1H)-one (200 mg, 0.55 mmol) and N,N-dimethylformamide dimethyl acetal (2.0 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 (2.0 mL) and phenylhydrazine (0.11 mL, 1.1 mmol) was added. This mixture was stirred at room temperature for 1 h, and then the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with AcOEt/MeOH (1/0 to 10/1) and recrystallized from iPr2O/AcOEt to give the title compound (141 mg, 55% yield) as a yellow solid: mp 182-183° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 2.98-3.22 (4H, m), 3.62-3.87 (7H, m), 6.78-6.92 (2H, m), 6.95 (1H, d, J=1.9 Hz), 7.21-7.54 (5H, m), 7.78 (1H, d, J=1.9 Hz), 8.48 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 466 [M+H]+. Anal. Calcd for C24H21F2N5O3: C, 61.93; H, 4.55; N, 15.05. Found: C, 61.90; H, 4.58; N, 14.87.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in AcOH (2.0 mL)
  4. stirringThis mixture was stirred at room temperature for 1 h
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with AcOEt/MeOH (1/0 to 10/1)
  8. customrecrystallized from iPr2O/AcOEt

Sources & evidence

ORD record
ord-e76b6b8aab7047899408f96c8cf6f52c
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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