反应详情

温度

0 °C

To a solution of 4-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-3,5-difluorobenzoic acid (Example 38, 204 mg, 0.49 mmol) in CH2Cl2 (1.5 mL) was added oxalyl chloride (93 mg, 0.74 mmol) and a catalytic amount of DMF at 0° C. After stirring at 0° C. for 5 min, the reaction was warmed to room temperature and stirred an additional for 30 min. The reaction was concentrated in vacuo and azeotrophed with toluene (2×). The crude material was dissolved in CH2Cl2 (1.5 mL) and was added to a solution of hydrazine (50 mmol) in CH2Cl2 (2 mL) at 0° C. After stirring for 15 min, the reaction was complete via LCMS analysis and the reaction was condensed to a solid, and azeotrophed with toluene (2×). The crude material was dissolved in trimethyl orthoacetate (5 mL) and methanol (2 mL) and heated to 120° C. for 1.5 hours. All volatile material was removed under reduced pressure and the crude material was purified via silica gel chromatography (100% EtOAc).

1. customat 0° C
2. temperaturethe reaction was warmed to room temperature
3. stirringstirred an additional for 30 min
4. concentrationThe reaction was concentrated in vacuo
5. dissolutionThe crude material was dissolved in CH2Cl2 (1.5 mL)
6. stirringAfter stirring for 15 min
7. customcondensed to a solid
8. customAll volatile material was removed under reduced pressure
9. customthe crude material was purified via silica gel chromatography (100% EtOAc)