تفاعل #1174958

معادلة التفاعل

4-dimethylamino-2-butanone

Sodium hydride

3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone

→

3-(4-dimethylamino-2-oxobutyl)-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone

المردود 24.7%

المذيبات

dimethylformamide

ethyl acetate

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىThe suspension obtained
2. 2
   workup.STIRRINGThe mixture is stirred for 3 hours at a temperature in the region of 20° C.
3. 3
   workup.ADDITIONis then poured
4. 4
   workup.DISTILLATIONinto distilled water (500 cc)
5. 5
   استخلاصextracted with dichloromethane (3×200 cc)
6. 6
   غسيلwashed with distilled water (4×25 cc)
7. 7
   تجفيفdried over magnesium sulphate
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
10. 10
    أخرىThe oily residue obtained
11. 11
    أخرىthe solution obtained
12. 12
    استخلاصis extracted with 1 N aqueous hydrochloric acid solution (2×100 cc)
13. 13
    غسيلwashed with ethyl acetate (50 cc)
14. 14
    استخلاصextracted with ethyl acetate (2×250 cc)
15. 15
    غسيلwashed with distilled water (3×30 cc)
16. 16
    تجفيفdried over magnesium sulphate
17. 17
    ترشيحfiltered
18. 18
    تركيزconcentrated to dryness under reduced pressure (2.7 kPa) at 60° C
19. 19
    أخرىAfter recrystallization in acetonitrile

الإجراء التجريبي

Sodium hydride (0.7 g) is added in small portions at a temperature in the region of -5° C. to a solution, maintained under an argon atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (8.0 g) in anhydrous dimethylformamide (125 cc). The suspension obtained is stirred for 30 minutes at a temperature in the region of -5° C. and then treated with a solution of 4-dimethylamino-2-butanone (3.5 g) in anhydrous dimethylformamide (5 cc). The mixture is stirred for 3 hours at a temperature in the region of 20° C., and is then poured into distilled water (500 cc) and extracted with dichloromethane (3×200 cc). The organic phases are combined, washed with distilled water (4×25 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The oily residue obtained is dissolved in ethyl acetate (400 cc) and the solution obtained is extracted with 1 N aqueous hydrochloric acid solution (2×100 cc). The aqueous phases are combined, washed with ethyl acetate (50 cc), alkalinized with 10 N aqueous sodium hydroxide solution to a pH in the region of 11 and extracted with ethyl acetate (2×250 cc). The organic phases are combined, washed with distilled water (3×30 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. After recrystallization in acetonitrile, 3-(4-dimethylamino-2-oxobutyl)-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (2.6 g), m.p. 140° C., is obtained.

المصدر