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

HRID 2387139Notes

Reaction equation

HRID 2387139 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

Conditions

Temperature
122.5 °C

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. additionwas added
  2. extractionThe mixture was extracted with dichloromethane (5×100 mL)
  3. washThe combined organic extracts were washed twice with water
  4. dry with materialdried with sodium sulfate
  5. customthe solvent evaporated
  6. customThe residue was purified chromatographically on silica gel with gradient elution from dichloromethane to methanol

Sources & evidence

ORD record
ord-74fb6ee4eb5b41caa1d8618b59be914d
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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