反应详情

温度

87 °C

Ethanol (1.8 mL) was added to 6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (195 mg, 0.342 mmol) followed by 12 N aqueous hydrochloric acid (1.8 mL, 21.8 mmol). The mixture was then heated to 87° C. for ca. 15 hours. The mixture was then cooled to room temperature, diluted with dichloromethane, and slowly neutralized with saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layers were extracted an additional time with dichloromethane. The organic layers were combined and dried by passing through a phase separator and then concentrated. The resulting residue was diluted with 1,2-dichloroethane (3.5 mL) and place at 0° C. Then N-chloromethylene-N,N-dimethyl ammonium chloride (Vilsmeier reagent) (85 mg, 067 mmol) was added. The resulting mixture was then heated to 35° C. After 5 minutes at 35° C. the mixture was diluted with dichloromethane, and slowly neutralized with saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layers were extracted an additional time with dichloromethane. The organic layers were combined and dried over Na2SO4, filtered and concentrated to furnish 4-chloro-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine without the need for further purification. MS (ESI+) m/z 575.3 (M+H)+.

1. temperatureThe mixture was then cooled to room temperature
2. customThe resulting layers were separated
3. extractionthe aqueous layers were extracted an additional time with dichloromethane
4. customdried
5. concentrationconcentrated
6. additionThe resulting residue was diluted with 1,2-dichloroethane (3.5 mL) and place at 0° C
7. additionThen N-chloromethylene-N,N-dimethyl ammonium chloride (Vilsmeier reagent) (85 mg, 067 mmol) was added
8. temperatureThe resulting mixture was then heated to 35° C
9. additionAfter 5 minutes at 35° C. the mixture was diluted with dichloromethane
10. customThe resulting layers were separated
11. extractionthe aqueous layers were extracted an additional time with dichloromethane
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated