反应详情

温度

20 °C

A solution of N-cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide (Example 1f, 0.15 g) in DCE (5 mL) was treated with 1-Boc-piperazine (0.19 g) and titanium(IV) isopropoxide (0.30 mL) under nitrogen. The resulting mixture was stirred at 20° C. for 16 h before adding sodium triacetoxyborohydride (0.28 g). The mixture was stirred at room temperature for 2 h before adding TFA (5 mL). The mixture stirred at room temperature for 2 h and evaporated to dryness. The mixture was quenched with 10% aq ammonia (5 mL) and extracted with ethyl acetate. The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Phenomenex Gemini column using a 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as eluent) to afford the title compound (0.065 g) as a white solid.

1. stirringThe mixture was stirred at room temperature for 2 h
2. stirringThe mixture stirred at room temperature for 2 h
3. customevaporated to dryness
4. customThe mixture was quenched with 10% aq ammonia (5 mL)
5. extractionextracted with ethyl acetate
6. dry with materialThe organic was dried (MgSO4)
7. filtrationfiltered
8. customevaporated
9. customto afford crude product
10. customThe crude product was purified by preparative HPLC (Phenomenex Gemini column