Phenylhydrazine → HCID 58072432, compound

HRID 1624767Notes

Reaction equation

HRID 1624767 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3](OCC)=O.C[O-].[Na+].[C:13]([C:16]1[C:21](=[O:22])[CH:20]=[CH:19][N:18]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[N:17]=1)(=O)[CH3:14].[C:33]1([NH:39][NH2:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(OC)(C)(C)C.C1COCC1.Cl.CC(O)=O>[C:33]1([N:39]2[C:13]([C:16]3[C:21](=[O:22])[CH:20]=[CH:19][N:18]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[N:17]=3)=[CH:14][C:3]([C:2]([F:1])([F:8])[F:9])=[N:40]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

9

Reactant 4

HCID 7516PhenylhydrazineHCID 9794Ethyl trifluoroacetateHCID 10942334Sodium MethoxideHCID 58072342HCID 58072342, compound

Product 1

HCID 58072432HCID 58072432, compoundYield 2%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolvent2×HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent2×

Procedure

To a solution of ethyl trifluoroacetate (0.139 mL, 1.17 mmol) in methyl tert-butyl ether (1 mL) was added NaOMe (28% in MeOH, 245 mg, 1.27 mmol) at room temperature. To the mixture was added a solution of 3-acetyl-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (300 mg, 1.06 mmol) in THF (1.5 mL) and methyl tert-butyl ether (1.5 mL) at room temperature. The mixture was stirred at room temperature for 2 days. The mixture was diluted with 1 M HCl aqueous solution, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. To the residue were added phenylhydrazine (0.209 mL, 2.12 mmol) and AcOH (3.5 mL). The mixture was heated to reflux for 90 min. The mixture was diluted with 1 M HCl aqueous solution, extracted with AcOEt, washed with NaHCO3 aqueous solution, dried over MgSO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/AcOEt=50/50 to 0/100), crystallized with AcOEt/hexane and purified by HPLC to yield the title compound (9.6 mg, 2% yield) as a white solid: mp 190-191° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 6.73 (1H, d, J=7.9 Hz), 7.37-7.81 (10H, m), 8.97 (1H, d, J=8.3 Hz). Anal. Calcd for C1H12F6N4O: C, 56.01; H, 2.69; N, 12.44. Found: C, 55.70; H, 2.81; N, 12.23.

Workup

  1. extractionextracted with AcOEt
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. temperatureThe mixture was heated
  7. temperatureto reflux for 90 min
  8. extractionextracted with AcOEt
  9. washwashed with NaHCO3 aqueous solution
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. custompurified by column chromatography on silica gel (hexane/AcOEt=50/50 to 0/100)
  14. customcrystallized with AcOEt/hexane
  15. custompurified by HPLC

Sources & evidence

ORD record
ord-ce8f5bd0b644416884456ac8aa210bda
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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