Реакция #94627

Уравнение реакции

sodium hydroxide

Cyclohexyl isocyanate

6-(7-chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine

triethylamine

→

6-(7-chloro-1,8-naphthyridin-2-yl)-5-cyclohexylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine

Выход 41.2%

Растворители

acetonitrile

ethanol

Условия реакции

Обработка

1. 1
   Температураthe reaction mixture is heated at the reflux temperature for 13 hours
2. 2
   ТемператураAfter cooling
3. 3
   Фильтрацияthe insoluble product is filtered off
4. 4
   Промывкаwashed successively with acetonitrile (2 × 10 cc.) and diisopropyl ether (2 × 20 cc.)
5. 5
   workup.DISSOLUTIONIt is then dissolved in methylene chloride (300 cc.)
6. 6
   Другоеthe solution obtained
7. 7
   ДругоеThe organic layer is decanted
8. 8
   Промывкаwashed with water (2 × 50 cc.)
9. 9
   Сушкаdried over anhydrous sodium sulphate in the presence of decolourising charcoal
10. 10
    Фильтрацияfiltered
11. 11
    Другоеevaporated to dryness under reduced pressure
12. 12
    ДругоеThe residue is recrystallised from acetonitrile (95 cc.)
13. 13
    Другоеthe product obtained
14. 14
    ДругоеThe insoluble product is then isolated from the boiling solution by filtration
15. 15
    Промывкаafter which it is washed with boiling ethanol (2 × 10 cc.)
16. 16
    ДругоеAfter drying

Методика

Cyclohexyl isocyanate (1.38 g.) is added 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 (3.12 g.) in anhydrous acetonitrile (60 cc.) in the presence of triethylamine (1 cc.), and the reaction mixture is heated at the reflux temperature for 13 hours. After cooling, the insoluble product is filtered off and washed successively with acetonitrile (2 × 10 cc.) and diisopropyl ether (2 × 20 cc.). It is then dissolved in methylene chloride (300 cc.) and the solution obtained is stirred for 15 minutes with 1N sodium hydroxide solution (50 cc.). The organic layer is decanted, washed with water (2 × 50 cc.), dried over anhydrous sodium sulphate in the presence of decolourising charcoal, filtered and then evaporated to dryness under reduced pressure. The residue is recrystallised from acetonitrile (95 cc.) and the product obtained is heated for 10 minutes with ethanol (65 cc.) at the reflux temperature. The insoluble product is then isolated from the boiling solution by filtration, after which it is washed with boiling ethanol (2 × 10 cc.). After drying, 6-(7-chloro-1,8-naphthyridin-2-yl)-5-cyclohexylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (1.8 g.), melting at 264° C., is obtained.

Источник