Potassium Carbonate → ethyl 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate

HRID 539889Notes

Reaction equation

HRID 539889 reaction equation
[CH3:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[N:24]=[C:23](Cl)[CH:22]=[CH:21][N:20]=1>CN(C)C=O>[Cl:18][C:19]1[N:24]=[C:23]([N:4]2[CH:5]=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:2]([CH3:1])=[N:3]2)[CH:22]=[CH:21][N:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 775312,4-DichloropyrimidineHCID 178469911HCID 178469911, compound

Product 1

HCID 86698981ethyl 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylateYield 52.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-methyl-1H-pyrazole-4-carboxylate (6.0 g, 38.9 mmol) in 50 mL of anhydrous N,N-dimethylformamide (DMF) were added potassium carbonate (10.8 g, 77.8 mmol) and 2,4-dichloropyrimidine (5.8 g, 38.9 mmol) at room temperature. The resulting suspension was stirred for 8 hours with monitoring a reaction with LC-MS or thin layer chromatography (TLC). Volatiles were removed and the residue was extracted with dichloromethane. The collected organic layer was washed with brine, 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 (5.45 g, 52%); MS (ESI) m/z 267 [M+H]+, 1H NMR (300 MHz, CDCl3) δ 8.99 (s, 1H), 8.68 (d, 1H, J=5.4 Hz), 7.86 (d, 1H, J=5.4 Hz), 4.35 (q, 2H, J=7.2 Hz), 2.57 (s, 3H), 1.40 (t, 3H, J=7.2 Hz).

Workup

  1. customa reaction with LC-MS or thin layer chromatography (TLC)
  2. customVolatiles were removed
  3. extractionthe residue was extracted with dichloromethane
  4. washThe collected organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by silica gel chromatography
  8. additiona mixture of heptanes and ethyl acetate

Sources & evidence

ORD record
ord-27eb9ebd561c4291b9dfe716dd9a22f7
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

Loading…