Water → 1-(2-Chlorophenyl)-n-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1h-pyrazole-5-carboxamide

HRID 2052798Notes

Reaction equation

HRID 2052798 reaction equation
[CH3:1][C:2]1[C:11]2[NH:10][C:9](=[O:12])O[C:7](=[O:13])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[C:25](C(Cl)=O)=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[N:22]1.[CH:33]([NH2:36])([CH3:35])[CH3:34].O>C(#N)C.N1C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[C:25]([C:9]([NH:10][C:11]2[C:6]([C:7]([NH:36][CH:33]([CH3:35])[CH3:34])=[O:13])=[CH:5][CH:4]=[CH:3][C:2]=2[CH3:1])=[O:12])=[CH:24][C:23]([C:29]([F:30])([F:31])[F:32])=[N:22]1

Participants

7

Reactant 4

HCID 962WaterHCID 6363IsopropylamineHCID 27598708-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dioneHCID 574582382-(2-Chloro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl chloride

Product 1

HCID 444044961-(2-Chlorophenyl)-n-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1h-pyrazole-5-carboxamideYield 72.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

To a sample of the title compound of Example 1, Step C (22.3 g, 0.126 mole), suspended in acetonitrile (100 mL) was added crude 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride (43 g). The mixture was diluted with 350 mL of pyridine and heated to approximately 95° C. for a period of 2 hours. The mixture was cooled to 29° C., then was treated with isopropylamine (32.2 mL, 0.38 mole). The reaction mass self-heated to 60° C. and was maintained at about 50° C. for one hour, then stirred overnight. The reaction mixture was poured into 1 L of water and stirred. The resulting solid was collected by filtration and washed with water. The wet cake was taken up in a mixture of dichloromethane and methanol, the water removed, and the organic phase was dried with molecular sieves and filtered. Volatiles were removed on a rotary evaporator. The crude product was triturated with 1:1 ether/hexane, collected by filtration and washed with hexanes to yield 42.6 g of a light tan solid melting at 230-231° C.

Workup

  1. temperatureThe mixture was cooled to 29° C.
  2. temperatureThe reaction mass self-heated to 60° C.
  3. temperaturewas maintained at about 50° C. for one hour
  4. stirringstirred
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with water
  7. additionThe wet cake was taken up in a mixture of dichloromethane and methanol
  8. customthe water removed
  9. customthe organic phase was dried with molecular sieves
  10. filtrationfiltered
  11. customVolatiles were removed on a rotary evaporator
  12. customThe crude product was triturated with 1:1 ether/hexane
  13. filtrationcollected by filtration
  14. washwashed with hexanes

Sources & evidence

ORD record
ord-ec51f960cb5a4031adabab0885b7381b
Source dataset
uspto-grants-2008_02
Patent number
US07326704B2

Reaction notes

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