反应详情

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).

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)