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

HRID 1503349Notes

Reaction equation

HRID 1503349 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 1 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-c303db04370949cb883c799fde7fbb07
Source dataset
uspto-grants-2015_12
Patent number
US09212178B2

Reaction notes

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