Reacción #1860483

Ecuación de reacción

5-chloro-1,2,3,4-tetrahydrobenzo[c]-2,7-naphthyridine

isopropanol tetrahydrofuran

triethylamine

dichloromethane methanol

→

title compound

Rendimiento 85.2%

1,2,3,4-tetrahydrobenzo[c]-2,7-naphthyridine

Rendimiento 85.2%

Disolventes

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe vessel was vacuum-degassed three times
2. 2
   Otroevacuated three times
3. 3
   workup.STIRRINGthe batch was stirred at ambient temperature for 16 hours
4. 4
   Lavadothe filter cake was rinsed with methanol (350 mL)
5. 5
   LavadoThe filtrate and rinse
6. 6
   Concentraciónwere concentrated
7. 7
   Otroto give a light yellow solid
8. 8
   Otrocollected on
9. 9
   Filtracióna filter
10. 10
    Otrodried to constant weight in a vacuum oven at 40° C
11. 11
    Otroobtained from the filtrate after it
12. 12
    Otropurified by chromatography
13. 13
    ConcentraciónThe filtrate was concentrated in vacuo
14. 14
    Otroto provide a solid, which
15. 15
    Otroto dry
16. 16
    Lavadoeluted with a gradient of 5 N ammoniacal methanol-dichloromethane
17. 17
    Concentraciónconcentrated under reduced pressure
18. 18
    Otroto obtain the product, which

Procedimiento

A 2 L heavy-walled glass Parr vessel equipped with a magnetic stirrer and stir bar was charged under nitrogen with 5-chloro-1,2,3,4-tetrahydrobenzo[c]-2,7-naphthyridine (30.0 g, 137 mmol), 2:1 (v/v) isopropanol-tetrahydrofuran (1100 mL), triethylamine (40.0 g, 395 mmol) and 10% by weight palladium on carbon (3.0 g). The vessel was vacuum-degassed three times, releasing the vacuum with nitrogen each time, and evacuated three times, pressurizing with hydrogen each time. The hydrogen pressure was adjusted to 55 psi and the batch was stirred at ambient temperature for 16 hours. The catalyst was filtered-off through Celite (40 g) and the filter cake was rinsed with methanol (350 mL). The filtrate and rinse were concentrated to give a light yellow solid. The solid was swished with 5:1 (v/v) dichloromethane-methanol (50 mL), collected on a filter and dried to constant weight in a vacuum oven at 40° C. This first crop material was blended with additional product obtained from the filtrate after it was in turn purified by chromatography. The filtrate was concentrated in vacuo to provide a solid, which was dissolved in a little methanol and loaded onto a 10 g KP-Sil samplet. The samplet was allowed to dry before inserting it into a 100 g KP-Sil SNAP cartridge that had been pre-equilibrated with 3 CV of 10% (v/v) 5 N ammoniacal methanol-dichloromethane. The cartridge was attached to a Biotage unit and eluted with a gradient of 5 N ammoniacal methanol-dichloromethane as follows: 10% v/v (2 CV), 10-14% v/v (5 CV), 14-16% v/v (4 CV), and 16-18% v/v (4 CV). Pure fractions were pooled and concentrated under reduced pressure to obtain the product, which was thoroughly blended with the first crop material to afford the title compound as a yellow solid (21.5 g, 85% yield).

Fuente