反应详情

温度

85 °C

A mixture of 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (320 mg, 0.862 mmol), tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (280 mg, 1.293 mmol) and DIPEA (0.226 mL, 1.293 mmol) in ACN (5 mL) was stirred at 85° C. overnight. UPLC indicated the presence of starting material, so the mixture was stirred at 85° C. overnight. UPLC showed about 50% conversion. Additional stirring at 85° C. for 3 d and at 100° C. overnight did not appreciably increase the conversion, so the reaction was stopped and the solvent was removed. The resulting crude material was reconstituted in MeOH/DMF (10 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (50%, 0.035% TFA). The collected fractions were combined and the ACN was removed via rotary evaporation. The resulting aqueous solution was neutralized with saturated aqueous NaHCO3, washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to give the title compound (51 mg, 11%). [M+H] calc'd for C26H32ClFN4O6, 552. found, 552.

1. stirringso the mixture was stirred at 85° C. overnight
2. stirringAdditional stirring at 85° C. for 3 d and at 100° C. overnight
3. temperaturedid not appreciably increase the conversion
4. customthe solvent was removed
5. custompurified via preparative HPLC
6. washeluting with water (0.05% TFA) and ACN (50%, 0.035% TFA)
7. customthe ACN was removed via rotary evaporation
8. washwashed with EtOAc (2×200 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customThe organic phase was stripped to dryness via rotary evaporation