m-Tolylhydrazinium(1+) chloride → 2-chloro-4-[1-(3-methylphenyl)-3-methyl-1H-pyrazol-5-yl]pyridine

HRID 1635511Notes

Reaction equation

HRID 1635511 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][N:14]=1)[CH2:5][C:6](=O)[CH2:7][C:8](=O)C.Cl.[CH3:16][C:17]1[CH:18]=[C:19]([NH:23][NH2:24])[CH:20]=[CH:21][CH:22]=1.[OH-].N>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([CH3:16])[CH:18]=3)[N:24]=[C:7]([CH3:8])[CH:6]=2)[CH:12]=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 71562m-Tolylhydrazinium(1+) chlorideHCID 21862953Ammonia hydroxideHCID 53955776HCID 53955776, compound

Product 1

HCID 114829832-chloro-4-[1-(3-methylphenyl)-3-methyl-1H-pyrazol-5-yl]pyridineYield 87%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of 1-(2-chloroisonicotinyl)-1,3-butanedione (1.35 g, 0.068 mol) and 3-methylphenylhydrazine hydrochloride (1.30 g, 0.0082 mol) in ethanol (40 mL) was added ammonia hydroxide (0.96 mL, 0.0082 mol) dropwise. The reaction mixture was heated at reflux overnight. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and the crude was purified by chromatography on silica gel (ethyl acetate/hexane, 2:8) to give 1.68 g (87% yield) of product as a yellow oil: Anal. Calcd. for C16H14ClN3: C, 67.72; H, 4.97; N, 14.81; Cl, 12.49. Found: C, 67.91; H, 5.08; N, 14.79; Cl, 12.40.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customThe solvent was removed
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customthe crude was purified by chromatography on silica gel (ethyl acetate/hexane, 2:8)

Sources & evidence

ORD record
ord-4b07217005f644799ac1019134ab52a2
Source dataset
uspto-grants-2003_01
Patent number
US06509361B1

Reaction notes

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