Triethylamine → N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide

HRID 589298Notes

Reaction equation

HRID 589298 reaction equation
[Cl:1][C:2]1[C:3]([CH2:12][CH:13]([NH2:15])[CH3:14])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:16][CH:17]([F:28])[C:18]1[C:22]([C:23](O)=[O:24])=[C:21]([F:26])[N:20]([CH3:27])[N:19]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[C:3]([CH2:12][CH:13]([NH:15][C:23]([C:22]2[C:18]([CH:17]([F:28])[F:16])=[N:19][N:20]([CH3:27])[C:21]=2[F:26])=[O:24])[CH3:14])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 231925843-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acidHCID 631964321-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-amine

Product 1

HCID 86685667N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamideYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At ambient temperature, 150 mg (0.545 mmol) of 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-amine, 116 mg (0.60 mmol) of 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acid, 81 mg (0.60 mmol) of 1-hydroxybenzotriazole and 55 mg (0.545 mmol) of triethylamine are stirred together in 1 ml of dimethylformamide until dissolution. This solution is pourred over a 2 g-containing basic alumina Chem-Elut™ cartridge packed with 1.48 g of Si-DCC resin (1.09 mmol of DCC per g of resin) and left overnight at ambient temperature. The cartridge is then washed three times by 2 ml of acetonitrile. The solvents are removed and the crude amide is purified by column chromatography on silica gel (gradient heptane/ethyl acetate) to yield 187 mg (78% yield) of N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide as yellow solid (M+H=415).

Workup

  1. additioncontaining basic alumina Chem-Elut™ cartridge
  2. washThe cartridge is then washed three times by 2 ml of acetonitrile
  3. customThe solvents are removed
  4. customthe crude amide is purified by column chromatography on silica gel (gradient heptane/ethyl acetate)

Sources & evidence

ORD record
ord-1603a5944f4f41a5935babcf7316e631
Source dataset
uspto-grants-2016_01
Patent number
US09232799B2

Reaction notes

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