反应详情

Dimethylcarbamoyl chloride (4.85 g.) and triethylamine (4.55 g.) are added successively to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (4.7 g.) in a mixture of anhydrous methylene chloride (47 cc.) and anhydrous pyridine (16 cc.). The reaction mixture is heated at the reflux temperature for 2 hours, and is then cooled and poured into water (180 cc.). A slight amount of insoluble matter is filtered off and the aqueous layer is decanted off and washed with methylene chloride (2 × 50 cc.) by successive decantations. The combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 30 cc.), dried with anhydrous sodium sulphate in the presence of decolourising charcoal, filtered and evaporated to dryness under reduced pressure. The residue obtained is taken up in acetonitrile (20 cc.) and the insoluble product is filtered off and washed with acetonitrile (3 × 2 cc.). Recrystallisation of this product from dimethylformamide (14 cc.) gives a solvated product (4.1 g.). This product is dissolved in dimethylformamide (100 cc.) at a temperature of about 70° C. The solution thus obtained is poured into water (1,200 cc.) and the insoluble product is filtered off and washed with water (5 × 20 cc.). After drying, 6-(7-chloro-1,8-naphthyridin-2-yl)-5-dimethylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (3.6 g.), melting at 270° C., is obtained.

1. temperatureThe reaction mixture is heated at the reflux temperature for 2 hours
2. temperatureis then cooled
3. filtrationA slight amount of insoluble matter is filtered off
4. customthe aqueous layer is decanted off
5. washwashed with methylene chloride (2 × 50 cc.) by successive decantations
6. washThe combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 30 cc.)
7. dry with materialdried with anhydrous sodium sulphate in the presence of decolourising charcoal
8. filtrationfiltered
9. customevaporated to dryness under reduced pressure
10. customThe residue obtained
11. filtrationthe insoluble product is filtered off
12. washwashed with acetonitrile (3 × 2 cc.)
13. customRecrystallisation of this product from dimethylformamide (14 cc.)
14. customgives a solvated product (4.1 g.)
15. customThe solution thus obtained
16. filtrationthe insoluble product is filtered off
17. washwashed with water (5 × 20 cc.)
18. customAfter drying