Dimethylformamide → 1-(5-trifluoromethylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamide

HRID 1748596Notes

Reaction equation

HRID 1748596 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([OH:19])=O.C[N:21](C)C=O.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([NH2:21])=[O:19]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 162278455-methyl-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 471413721-(5-trifluoromethylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylic acid (3.0 g) described in Reference Example 8 in toluene (37 ml) were added N,N-dimethylformamide (catalytic amount) and thionyl chloride (2.2 ml), stirred at 80° C. for 8.5 hours, and then the solvent was evaporated in vacuo. To a solution of the residue in pyridine (20 ml) was added a solution of 4-(5-aminopyridin-2-yl)piperidine-1-carboxylic acid tert-butyl ester (2.8 g) in pyridine (17 ml), stirred at 80° C. for 5 hours, then additionally, 5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylic acid chloride (980 mg) described in Reference Example 180 was added thereto, and stirred at 80° C. for 2 hours. To the reaction solution was added triethylamine (4.2 ml), then water was added thereto, and the precipitated solid was washed with water and ethyl acetate to give N-[6-O-tert-butyloxycarbonylpiperidin-4-yl)pyridin-3-yl]-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (4.0 g) as a yellow solid.

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionTo a solution of the residue in pyridine (20 ml) was added a solution of 4-(5-aminopyridin-2-yl)piperidine-1-carboxylic acid tert-butyl ester (2.8 g) in pyridine (17 ml)
  3. stirringstirred at 80° C. for 5 hours
  4. additionwas added
  5. stirringstirred at 80° C. for 2 hours
  6. additionTo the reaction solution was added triethylamine (4.2 ml)
  7. additionwater was added
  8. washthe precipitated solid was washed with water and ethyl acetate

Sources & evidence

ORD record
ord-173a6fe57fab4101ba3713a94c37f9c4
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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