Diisopropylethylamine → N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide

HRID 1843055Notes

Reaction equation

HRID 1843055 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:14])=[C:6]([CH:13]=1)[C:7]([NH:9][CH:10]1[CH2:12][CH2:11]1)=[O:8].C(N(C(C)C)C(C)C)C.[CH3:24][N:25]1[C:29]([C:30](Cl)=[O:31])=[C:28]([C:33]([F:36])([F:35])[F:34])[C:27]([C:37]([F:43])([F:42])[C:38]([F:41])([F:40])[F:39])=[N:26]1>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:14][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:30]([C:29]2[N:25]([CH3:24])[N:26]=[C:27]([C:37]([F:42])([F:43])[C:38]([F:40])([F:41])[F:39])[C:28]=2[C:33]([F:35])([F:36])[F:34])=[O:31])=[CH:13][C:6]=1[C:7](=[O:8])[NH:9][CH:10]1[CH2:11][CH2:12]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 167752405-amino-2-chloro-N-cyclopropylbenzamideHCID 866600741-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride

Product 1

HCID 46219548N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

Procedure

95.3 mg (0.45 mmol) of 5-amino-2-chloro-N-cyclopropylbenzamide, 3.7 mg (0.03 mmol) of N,N-dimethylpyridine-4-amine are dissolved in 2.5 ml of ethyl acetate. The solution is cooled to 0° C. using an ice bath and admixed with 158 μl (0.91 mmol) of N-ethyldiisopropylamine. 100 mg (0.30 mmol) of 1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride are suspended in 2.5 ml of ethyl acetate and then added to the cooled reaction solution. The reaction mixture is heated for four hours at 50° C. and then stirred for 16 hours at room temperature. The reaction solution is diluted with 10.0 ml of ethyl acetate. The organic phase is washed three times with 1M hydrochloric acid, twice with 1M sodium hydroxide solution and once with saturated sodium chloride solution. The organic phase is dried over sodium sulphate and filtered and solvent is removed under reduced pressure on a rotary evaporator. This gives 151 mg of N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (97%) as white solid.

Workup

  1. additionadded to the cooled reaction solution
  2. temperatureThe reaction mixture is heated for four hours at 50° C.
  3. washThe organic phase is washed three times with 1M hydrochloric acid
  4. dry with materialThe organic phase is dried over sodium sulphate
  5. filtrationfiltered
  6. customsolvent is removed under reduced pressure on a rotary evaporator

Sources & evidence

ORD record
ord-2e494e041f1f4a8cb643c7e9531674fd
Source dataset
uspto-grants-2015_02
Patent number
US08946234B2

Reaction notes

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