反应详情

温度

20 °C

3-Dimethylaminopropionic acid hydrochloride 9.2 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (16.7 g) are added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (16.5 g) in anhydrous dimethylformamide (100 cc), and the suspension obtained is stirred for 24 hours at a temperature in the region of 20° C. Distilled water (200 cc) and dichloromethane (200 cc) are then added. The aqueous phase is separated after settling has occurred and then re-extracted with dichloromethane (3×50 cc). The organic phases are combined, washed with distilled water (2×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 80° C. The residue obtained is dissolved in dichloromethane (100 cc) and the solution extracted with 1N aqueous hydrochloric acid solution (2×100 cc). The aqueous phases are combined, washed with dichloromethane (50 cc), alkalinized with 10 N sodium hydroxide solution to a pH in the region of 11 and extracted with dichloromethane (2×150 cc). The organic phases are combined, washed with distilled water (2×30 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. After the product thereby obtained has been recrystallized twice successively in ethanol, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 3-dimethylaminopropionate (2.9 g), m.p. 150° C., is obtained.

1. customthe suspension obtained
2. customThe aqueous phase is separated after settling
3. extractionre-extracted with dichloromethane (3×50 cc)
4. washwashed with distilled water (2×50 cc)
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 80° C
8. customThe residue obtained
9. extractionthe solution extracted with 1N aqueous hydrochloric acid solution (2×100 cc)
10. washwashed with dichloromethane (50 cc)
11. extractionextracted with dichloromethane (2×150 cc)
12. washwashed with distilled water (2×30 cc)
13. dry with materialdried over magnesium sulphate
14. filtrationfiltered
15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 60° C
16. customAfter the product thereby obtained
17. customhas been recrystallized twice successively in ethanol