Reacción #73054

Ecuación de reacción

4-morpholinecarbonyl chloride

triethylamine

4-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]piperidin-4-ol dihydrochloride

4-Morpholinecarbonyl chloride

→

4-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]-1-(morpholin-4-ylcarbonyl)piperidin-4-ol

Rendimiento 88.3%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato slowly warm to ambient temperature
2. 2
   workup.WAITat 30° C. for 2 days
3. 3
   workup.STIRRINGthe reaction mixture was stirred at 30° C. for 5 days
4. 4
   ConcentraciónThe reaction mixture was concentrated under reduced pressure
5. 5
   OtroThe residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
6. 6
   LavadoThe organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
7. 7
   Secadodried over sodium sulfate
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated under reduced pressure
10. 10
    Otroto provide an off white solid
11. 11
    OtroThis material was triturated with acetonitrile
12. 12
    Otrorecrystallized from chloroform/hexanes
13. 13
    Otroisolated by filtration
14. 14
    Lavadowashed with hexanes
15. 15
    Otrodried under high vacuum at 130° C.

Procedimiento

Under a nitrogen atmosphere triethylamine (1.39 mL, 10.0 mmol) was added to a suspension of 4-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]piperidin-4-ol dihydrochloride (1.00 g, 2.50 mmol) in dichloromethane (25 mL). The mixture was cooled to −5° C. 4-Morpholinecarbonyl chloride (292 μL, 2.50 mmol) was added and the reaction mixture was allowed to slowly warm to ambient temperature. The reaction mixture was stirred at ambient temperature for 2 days and then at 30° C. for 2 days. More 4-morpholinecarbonyl chloride (30 μL) was added and the reaction mixture was stirred at 30° C. for 5 days. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL). The organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL), dried over sodium sulfate, filtered, and then concentrated under reduced pressure to provide an off white solid. This material was triturated with acetonitrile, recrystallized from chloroform/hexanes, isolated by filtration, washed with hexanes, and dried under high vacuum at 130° C. to provide 0.97 g of 4-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]-1-(morpholin-4-ylcarbonyl)piperidin-4-ol as a white powder, mp>255.0° C. Anal. Calcd for C22H29N7O3.0.25H2O C, 59.51; H, 6.70; N, 22.08. Found: C, 59.32; H, 6.36; N, 22.00.

Fuente