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

HRID 589300Notes

Reaction equation

HRID 589300 reaction equation
[F:1][CH:2]([F:13])[C:3]1[C:7]([C:8](Cl)=[O:9])=[C:6]([F:11])[N:5]([CH3:12])[N:4]=1.[Cl:14][C:15]1[C:16]([CH2:25][CH:26]([NH:28][CH:29]2[CH2:31][CH2:30]2)[CH3:27])=[N:17][CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1.C(N(CC)CC)C>O1CCCC1>[Cl:14][C:15]1[C:16]([CH2:25][CH:26]([N:28]([CH:29]2[CH2:31][CH2:30]2)[C:8]([C:7]2[C:3]([CH:2]([F:13])[F:1])=[N:4][N:5]([CH3:12])[C:6]=2[F:11])=[O:9])[CH3:27])=[N:17][CH:18]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 529205085-fluoro-1-methyl-3-difluoromethyl-1H-pyrazole-4-carbonyl chlorideHCID 86685669N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}cyclopropanamine

Product 1

HCID 86685668N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamideYield 49.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At ambient temperature, a solution of 74 mg (0.35 mmol) of 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carbonyl chloride in 2 ml of tetrahydrofurane is added dropwise to a solution of 100 mg (0.317 mmol) of N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}cyclopropanamine and 0.137 ml (0.984 mmol) of triethylamine in 3 ml of tetrahydrofurane. The reaction mixture is stirred for 15 hrs at ambient temperature. The solvent is removed under vacuum and 50 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×25 ml) and the combined organic layers are successively washed by a 1 N solution of HCl, a saturated solution of potassium carbonate and brine and dried over magnesium sulfate to yield after concentration 131 mg of an oil. Column chromatography on silica gel (gradient heptane/ethyl acetate) yields 72 mg (47% yield) of N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide as a colorless oil (M+H=455).

Workup

  1. customThe solvent is removed under vacuum and 50 ml of water
  2. additionare then added to the residue
  3. extractionThe watery layer is extracted twice with ethyl acetate (2×25 ml)
  4. washthe combined organic layers are successively washed by a 1 N solution of HCl
  5. dry with materiala saturated solution of potassium carbonate and brine and dried over magnesium sulfate
  6. customto yield after concentration 131 mg of an oil

Sources & evidence

ORD record
ord-02447e021a694ee78c953b1439e36da9
Source dataset
uspto-grants-2016_01
Patent number
US09232799B2

Reaction notes

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