Reacción #94627

Ecuación de reacción

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

Rendimiento 41.2%

Disolventes

acetonitrile

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction mixture is heated at the reflux temperature for 13 hours
2. 2
   TemperaturaAfter cooling
3. 3
   Filtraciónthe insoluble product is filtered off
4. 4
   Lavadowashed 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
   Otrothe solution obtained
7. 7
   OtroThe organic layer is decanted
8. 8
   Lavadowashed with water (2 × 50 cc.)
9. 9
   Secadodried over anhydrous sodium sulphate in the presence of decolourising charcoal
10. 10
    Filtraciónfiltered
11. 11
    Otroevaporated to dryness under reduced pressure
12. 12
    OtroThe residue is recrystallised from acetonitrile (95 cc.)
13. 13
    Otrothe product obtained
14. 14
    OtroThe insoluble product is then isolated from the boiling solution by filtration
15. 15
    Lavadoafter which it is washed with boiling ethanol (2 × 10 cc.)
16. 16
    OtroAfter drying

Procedimiento

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.

Fuente