Triethylamine → N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-{1-[methyl(phenyl)-amino]propan-2-yl}-1H-pyrazole-4-carboxamide

HRID 77695Notes

Reaction equation

HRID 77695 reaction equation
[F:1][CH:2]([F:12])[C:3]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]([CH3:11])[N:4]=1.[CH:13]1([NH:16][CH:17]([CH3:27])[CH2:18][N:19]([CH3:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.C(N(CC)CC)C.CCCCCCC.C(OCC)(=O)C>O1CCCC1>[CH:13]1([N:16]([CH:17]([CH3:27])[CH2:18][N:19]([CH3:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:8]([C:7]2[C:3]([CH:2]([F:12])[F:1])=[N:4][N:5]([CH3:11])[CH:6]=2)=[O:9])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 21899848Ethylacetate heptaneHCID 68557675N2-cyclopropyl-N1-methyl-N1-phenylpropane-1,2-diamine

Product 1

HCID 67071695N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-{1-[methyl(phenyl)-amino]propan-2-yl}-1H-pyrazole-4-carboxamideYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At ambient temperature, a solution of 220 mg (1.13 mmol) of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a solution of 210 mg (1.03 mmol) of N2-cyclopropyl-N1-methyl-N1-phenylpropane-1,2-diamine and 0.16 ml (1.13 mmol) of triethylamine in 5 ml of tetrahydrofurane. The reaction mixture is stirred for 15 hrs at room temperature. The solvent to is removed under vacuum and 100 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×150 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 filtered over a ChemElut cartridge to yield after concentration 180 mg of a brown oil. Column chromatography (gradient heptane/ethyl acetate) yielded 150 mg (38% yield) of N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-{1-[methyl(phenyl)-amino]propan-2-yl}-1H-pyrazole-4-carboxamide as a yellow oil (M+H=363).

Workup

  1. customThe solvent to is removed under vacuum and 100 ml of water
  2. additionare then added to the residue
  3. extractionThe watery layer is extracted twice with ethyl acetate (2×150 ml)
  4. washthe combined organic layers are successively washed by a 1 N solution of HCl
  5. filtrationa saturated solution of potassium carbonate and brine and filtered over a ChemElut cartridge
  6. customto yield after concentration 180 mg of a brown oil

Sources & evidence

ORD record
ord-190cce6815b146d6958063d1e972cc95
Source dataset
uspto-grants-2014_09
Patent number
US08841332B2

Reaction notes

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