Methylhydrazine → 5-Amino-3-cyclohexyl-1-methyl-1H-pyrazole-4-carbonitrile

HRID 548776Notes

Reaction equation

HRID 548776 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].[H-].[Na+].[CH:8]1([C:14](Cl)=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.S(OC)(OC)(=O)=O.C(N(CC)CC)C.[CH3:31][NH:32][NH2:33]>O1CCCC1>[NH2:4][C:3]1[N:32]([CH3:31])[N:33]=[C:14]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[C:2]=1[C:1]#[N:5]

Participants

8

Reactant 6

HCID 6061MethylhydrazineHCID 6497Dimethyl SulfateHCID 8010MalononitrileHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 75938Cyclohexanecarbonyl chloride

Product 1

HCID 230243275-Amino-3-cyclohexyl-1-methyl-1H-pyrazole-4-carbonitrileYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 17.2 g (260 mmol) of malononitrile in 260 mL of tetrahydrofuran was added slowly to 20.8 g (60% dispersion in mineral oil; 520 mmol) of sodium hydride at 0° C., then, to this mixture was added by dripping 35 mL (260 mmol) of cyclohexanecarbonyl chloride at the same temperature and the mixture was stirred for 1.5 hours at room temperature. Then, 30 mL (312 mmol) of dimethyl sulfate was added to the reaction mixture and the mixture was refluxed for 3 hours. Then, 17.4 mL (125 mmol) of triethylamine and 13.8 mL (260 mmol) of methylhydrazine were added to the reaction mixture under ice cooling and the mixture was refluxed for 1 hour. After the mixture was cooled to the room temperature, the solvent was removed under reduce pressure. Water was added to the residue and the mixture was extracted with ethyl acetate and the organic layer was washed with water, and saturated saline solution, then, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1 to 20/1). The obtained crude crystalline was further purified by recrystallization (hexane-ethyl acetate) to give 20.7 g (39%) of the title compound. The filtrate was further purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2: 1) to give 11.3 g (21%) of the title compound.

Workup

  1. additionto this mixture was added
  2. temperaturethe mixture was refluxed for 3 hours
  3. temperaturethe mixture was refluxed for 1 hour
  4. temperatureAfter the mixture was cooled to the room temperature
  5. customthe solvent was removed
  6. additionWater was added to the residue
  7. extractionthe mixture was extracted with ethyl acetate
  8. washthe organic layer was washed with water, and saturated saline solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customthe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1 to 20/1)
  12. customThe obtained crude
  13. customcrystalline was further purified by recrystallization (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-fc2a602b6a7e492593d0f58ea3d465b1
Source dataset
uspto-grants-2011_05
Patent number
US07943624B2

Reaction notes

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