反应详情

A solution of 5-methyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (75 mg, 0.194 mmol), diisopropylethylamine (135 μL, 0.775 mmol), HATU (73.7 mg, 0.194 mmol) and (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (79.0 mg, 0.233 mmol, see Example C) in DMF (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo. The resulting residue was redissolved in THF (5 mL) and treated with an aqueous solution of LiOH (2 mL, 0.5M) for 30 minutes. Next, the solvent was removed, and the resulting residue was suspended in EtOAc (50 mL) and washed with water (2×10 mL). The dried (MgSO4) organic phase was concentrated in vacuo, and the resulting residue was purified by reverse phase chromatography (Biotage, C-18 12M+) on Biotage SP4 unit using a gradient of 5-80% CH3CN/water to provide (S)-tert-butyl 2-((S)-1-(4-chlorophenyl)-2-(4-(5-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (70 mg, 0.130 mmol, 67.0% yield) as a solid after drying under high vacuum. LCMS (APCI+) m/z 539.2, 541.2 (M+H)+.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionThe resulting residue was redissolved in THF (5 mL)
3. additiontreated with an aqueous solution of LiOH (2 mL, 0.5M) for 30 minutes
4. customNext, the solvent was removed
5. washwashed with water (2×10 mL)
6. dry with materialThe dried (MgSO4) organic phase
7. concentrationwas concentrated in vacuo
8. customthe resulting residue was purified by reverse phase chromatography (Biotage