4-(Trifluoromethyl)benzoic acid → HCID 58071748, compound

HRID 1631905Notes

Reaction equation

HRID 1631905 reaction equation
C([O:5][C:6](=[O:25])[CH2:7][C:8]1[C:9]([CH2:23][CH3:24])=[N:10][N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]=1[CH2:13][CH3:14])(C)(C)C.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[CH2:23]([C:9]1[C:8]([CH2:7][C:6]([OH:5])=[O:25])=[C:12]([CH2:13][CH3:14])[N:11]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:32](=[O:33])[C:31]3[CH:35]=[CH:36][C:28]([C:27]([F:26])([F:37])[F:38])=[CH:29][CH:30]=3)=[CH:20][CH:21]=2)[N:10]=1)[CH3:24]

Participants

7

Reactant 5

HCID 99664-(Trifluoromethyl)benzoic acidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66707286HCID 66707286, compound2×

Product 1

HCID 58071748HCID 58071748, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Coupling: To a solution of [1-(4-amino-benzyl)-3,5-diethyl-1H-pyrazol-4-yl]-acetic acid tert-butyl ester (intermediate 2.1.2, 99 mg, 0.29 mmol) in dimethylformamide (1.5 mL) was added 4-(trifluoromethyl)benzoic acid (67 mg, 0.34 mmol), diisopropylethylamine (90 μL, 0.53 mmol) and TBTU (82 mg, 0.25 mmol). The reaction mixture was stirred for 18 h at room temperature. The reaction mixture was treated with aqueous K2CO3 solution (2 M, 0.15 mL) and filtered over Alox B, eluting with 10% methanol in dichloromethane. Cleavage of tert-butyl ester: The volatiles were removed under reduced pressure and the residue was treated with trifluoroacetic acid (2 mL). After 42 h, the mixture was concentrated under reduced pressure and purified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3).

Workup

  1. filtrationfiltered over Alox B
  2. washeluting with 10% methanol in dichloromethane
  3. customCleavage of tert-butyl ester: The volatiles were removed under reduced pressure
  4. additionthe residue was treated with trifluoroacetic acid (2 mL)
  5. waitAfter 42 h
  6. concentrationthe mixture was concentrated under reduced pressure
  7. custompurified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3)

Sources & evidence

ORD record
ord-595de646f3cc4ef5a1c6a8044b97e662
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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