反应详情

2,5-dichloro-3-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile (90 mg, 0.265 mmol) and lithium tert-butoxide (22 mg, 0.278 mmol) were dissolved in DMF (1 mL) and the solution stirred for 5 minutes at room temperature. The reaction mixture was cooled to 0° C. and 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine (112 mg, 0.265 mmol) in DMF (1.5 mL) was added. After the addition, the solution was allowed to warm to room temperature and stirred for 16 hours, after which saturated aqueous ammonium chloride (1 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The combined organic fractions were washed with water (3×15 mL). The combined aqueous layers were back-extracted with EtOAc (25 mL) and the extracts subsequently washed with water (3×15 mL). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (12 g) eluting with 0-40% EtOAc/hexanes to afford the title compound. LRMS (M+1)=726.3.

1. temperatureThe reaction mixture was cooled to 0° C.
2. additionAfter the addition
3. temperatureto warm to room temperature
4. stirringstirred for 16 hours
5. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
6. washThe combined organic fractions were washed with water (3×15 mL)
7. extractionThe combined aqueous layers were back-extracted with EtOAc (25 mL)
8. washthe extracts subsequently washed with water (3×15 mL)
9. dry with materialThe combined organic fractions were dried (MgSO4)
10. filtrationfiltered
11. customthe solvent was evaporated under reduced pressure
12. customThe resulting residue was purified by column chromatography on silica gel (12 g)
13. washeluting with 0-40% EtOAc/hexanes