4-(Trifluoromethyl)benzoic acid → {3,5-Dimethyl-1-[4-(4-trifluoromethyl-benzoylamino)-benzyl]-1H-pyrazol-4-yl}-acetic acid

HRID 1631903Notes

Reaction equation

HRID 1631903 reaction equation
C[O:2][C:3](=[O:20])[CH2:4][C:5]1[C:6]([CH3:19])=[N:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[C:9]=1[CH3:10].[F:21][C:22]([F:33])([F:32])[C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=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>[CH3:19][C:6]1[C:5]([CH2:4][C:3]([OH:2])=[O:20])=[C:9]([CH3:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:27](=[O:28])[C:26]3[CH:30]=[CH:31][C:23]([C:22]([F:21])([F:32])[F:33])=[CH:24][CH:25]=3)=[CH:14][CH:13]=2)[N:7]=1

Participants

7

Reactant 5

HCID 99664-(Trifluoromethyl)benzoic acidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester2×

Product 1

HCID 58071835{3,5-Dimethyl-1-[4-(4-trifluoromethyl-benzoylamino)-benzyl]-1H-pyrazol-4-yl}-acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Coupling: To a solution of [1-(4-amino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 1.1.3, 85 mg, 0.26 mmol) in dimethylformamide (1 mL) was added 4-(trifluoromethyl)benzoic acid (62 mg, 0.32 mmol), diisopropylethylamin (90 μL, 0.53 mmol) and TBTU (94 mg, 0.29 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. Saponification: The volatiles were removed under reduced pressure and the remaining residue was treated with aqueous NaOH solution (4 M, 0.2 mL). The mixture was 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. customSaponification: The volatiles were removed under reduced pressure
  4. additionthe remaining residue was treated with aqueous NaOH solution (4 M, 0.2 mL)
  5. customThe mixture was purified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3)

Sources & evidence

ORD record
ord-4ea5eab7c51740ac81585ea35e82f8b0
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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