Dimethylformamide → 1-(6-Bromopyridin-3-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid ethyl ester

HRID 1644003Notes

Reaction equation

HRID 1644003 reaction equation
[CH2:1]([C:4]1[CH:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[NH:6][N:5]=1)[CH2:2][CH3:3].[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21]Br)=[CH:17][N:16]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.C([O-])(O)=O.[Na+]>C(OCC)C>[CH2:12]([O:11][C:9]([C:7]1[CH:8]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:21][C:18]2[CH:17]=[N:16][C:15]([Br:14])=[CH:20][CH:19]=2)[N:6]=1)=[O:10])[CH3:13]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 64246602-Bromo-5-bromomethylpyridineHCID 178439317HCID 178439317, compound

Product 1

HCID 581029001-(6-Bromopyridin-3-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Ethyl 3-n-propylpyrazole-5-carboxylate (1.7 g, 9.1 mmol), 2-bromo-5-bromomethylpyridine (4.6 g, 9.1 mmol) and potassium carbonate (1.8 g, 12.7 mmol) were dissolved in DMF (70.0 mL, 904 mmol). The resulting suspension was stirred at room temperature overnight. The material was diluted with aqueous. NaHCO3 and diethyl ether. The aqueous layer was further extracted with diethyl ether. The combined organics were dried over MgSO4, filtered and concentrated. The residue was purified using flash chromatography [1st 30:1 hexanes/EtOAc; 2nd 10:1 hexanes/EtOAc]. The two isomers were separated and analyzed by NMR and NOE: 1-(6-bromopyridin-3-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid ethyl ester (1.2 g) and 2-(6-bromopyridin-3-ylmethyl)-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester.

Workup

  1. additionThe material was diluted with aqueous
  2. extractionThe aqueous layer was further extracted with diethyl ether
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified
  7. customThe two isomers were separated

Sources & evidence

ORD record
ord-77d085f3338646939d34dc0ec3524224
Source dataset
uspto-grants-2012_02
Patent number
US08119634B2

Reaction notes

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