Methanol → HCID 58072381, compound

HRID 2089956Notes

Reaction equation

HRID 2089956 reaction equation
[C:1]([C:5]1[C:10](=[O:11])[CH:9]=[CH:8][N:7]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:6]=1)(=O)[CH2:2][CH3:3].[CH3:22][O-].[Na+].[C:25]1([NH:31][NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CO>C(OC)=O.O.Cl>[CH3:3][C:2]1[CH:22]=[N:32][N:31]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:1]=1[C:5]1[C:10](=[O:11])[CH:9]=[CH:8][N:7]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:6]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 7516PhenylhydrazineHCID 10942334Sodium MethoxideHCID 58072182HCID 58072182, compound

Product 1

HCID 58072381HCID 58072381, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 7865Methyl formateSolvent

Procedure

To a suspension of 3-propanoyl-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (384 mg, 1.30 mmol) in methyl formate (3.8 mL) was added NaOMe (28% in MeOH, 326 mg, 1.69 mmol) at room temperature. The mixture was stirred at room temperature for 3.5 h. The mixture was diluted with water and 1 M HCl aqueous solution, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, concentrated in vacuo and crystallized with AcOEt/hexane. To the solid were added phenylhydrazine (0.405 mL, 4.12 mmol) and MeOH (6.7 mL). The mixture was heated to reflux for 15 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 silica gel (hexane/AcOEt=50/50 to 0/100) and crystallized with AcOEt/heptane to yield the title compound (161 mg, 39% yield) as a pale yellow solid: mp 208-211° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.09 (3H, s), 6.62 (1H, d, J=8.0 Hz), 7.26-7.35 (3H, m), 7.35-7.44 (2H, m), 7.64-7.85 (5H, m), 8.95 (1H, d, J=8.2 Hz). Anal. Calcd for C21H15F3N4O: C, 63.63; H, 3.81; N, 14.14. Found: C, 63.46; H, 3.92; N, 13.98.

Workup

  1. extractionextracted with AcOEt
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customcrystallized with AcOEt/hexane
  7. temperatureThe mixture was heated
  8. temperatureto reflux for 15 h
  9. extractionextracted with AcOEt
  10. washwashed with saturated NaHCO3 aqueous solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. custompurified by column chromatography on silica gel (hexane/AcOEt=50/50 to 0/100)
  15. customcrystallized with AcOEt/heptane

Sources & evidence

ORD record
ord-43bfa52f3235437691f8cd0873159a31
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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