Potassium Carbonate → 1,3-dimethyl-5-(4-methylpiperazin-1-yl)-1H-pyrazole-4-carbaldehyde

HRID 859748Notes

Reaction equation

HRID 859748 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[CH:9]=[O:10].[CH3:11][N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+]>CN(P(N(C)C)(N(C)C)=O)C.O>[CH3:7][N:6]1[C:2]([N:15]2[CH2:16][CH2:17][N:12]([CH3:11])[CH2:13][CH2:14]2)=[C:3]([CH:9]=[O:10])[C:4]([CH3:8])=[N:5]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 27773975-Chloro-1,3-dimethylpyrazole-4-carboxaldehyde

Product 1

HCID 337871101,3-dimethyl-5-(4-methylpiperazin-1-yl)-1H-pyrazole-4-carbaldehydeYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of 5-chloro-1,3-dimethyl-1H-pyrazole-4-carbaldehyde (25.4 g, 0.16 mol) in HMPA (25 mL) and water (25 mL) was added 1-methylpiperazine (40 g, 0.4 mol, 2.5 equiv), and the mixture was heated at 120–125° C. for 25 h. When the reaction was completed, the reaction mixture was poured into water (500 mL), and potassium carbonate was added to make the medium strongly alkaline. The mixture was extracted with dichloromethane (5×100 mL). The combined organic extracts were washed twice with water and dried with sodium sulfate, and the solvent evaporated. The residue was purified chromatographically on silica gel with gradient elution from dichloromethane to methanol, affording 10.2 g (29%) of the title product. Satisfactory C,H,N-analysis was obtained. 1H NMR (400 MHz, DMSO-d6): δ 2.23 (s, 3H), 2.26 (s, 3H), 2.44 (m, 4H), 3.16 (m, 4H), 3.59 (s, 3H), 9.88 (s, 1H). LC-MS (API-ES) calcd for C11H18N4O: 222.15, found (M+H+): 223.1 m/z.

Workup

  1. temperaturethe mixture was heated at 120–125° C. for 25 h
  2. additionwas added
  3. extractionThe mixture was extracted with dichloromethane (5×100 mL)
  4. washThe combined organic extracts were washed twice with water
  5. dry with materialdried with sodium sulfate
  6. customthe solvent evaporated
  7. customThe residue was purified chromatographically on silica gel with gradient elution from dichloromethane to methanol

Sources & evidence

ORD record
ord-3631a6646e4f4892a145953696fd8fe7
Source dataset
uspto-grants-2006_12
Patent number
US07151105B2

Reaction notes

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