Potassium Carbonate → 1-(2-Chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde

HRID 539890Notes

Reaction equation

HRID 539890 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([CH3:10])=[N:4]1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Cl:17][C:18]1[N:23]=C(Cl)C=[CH:20][N:19]=1>CN(C)C=O.C(OCC)(=O)C>[Cl:17][C:18]1[N:23]=[C:1]([N:3]2[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([CH3:10])=[N:4]2)[CH:2]=[CH:20][N:19]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 775312,4-DichloropyrimidineHCID 5732031-ethyl-3-methyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 730123151-(2-Chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehydeYield 42.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 3-methyl-1H-pyrazole-4-carbaldehyde (6.4 g, 58.0 mmol) in 60 mL of anhydrous N,N-dimethylformamide were added potassium carbonate (10.8 g, 77.8 mmol) and 2,4-dichloropyrimidine (8.64 g, 58.0 mmol) at room temperature. The resulting suspension was stirred for 14 hours at room temperature with monitoring a reaction with LC-MS or thin layer chromatography (TLC). The reaction mixture was diluted with ethyl acetate and washed with brine (×2). The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography using a mixture of heptanes and ethyl acetate to afford the desired intermediate 2 as a white solid (5.47 g, 42%); MS (ESI) m/z 223 [M+H]+, 1H NMR (300 MHz, CDCl3) δ 10.06 (s, 1H), 9.04 (s, 1H), 8.70 (d, 1H, J=5.4 Hz), 7.87 (1H, d, J=5.4 Hz), 2.59 (s, 3H).

Workup

  1. customa reaction with LC-MS or thin layer chromatography (TLC)
  2. washwashed with brine (×2)
  3. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by silica gel chromatography
  6. additiona mixture of heptanes and ethyl acetate

Sources & evidence

ORD record
ord-d9c3f87b6352464680f0a2cf2c07943f
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

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