Réaction #73054

Équation de réaction

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

Rendement 88.3%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Températureto 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
   ConcentrationThe reaction mixture was concentrated under reduced pressure
5. 5
   AutreThe residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
6. 6
   LavageThe organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
7. 7
   Séchagedried over sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    Autreto provide an off white solid
11. 11
    AutreThis material was triturated with acetonitrile
12. 12
    Autrerecrystallized from chloroform/hexanes
13. 13
    Autreisolated by filtration
14. 14
    Lavagewashed with hexanes
15. 15
    Autredried under high vacuum at 130° C.

Mode opératoire

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.

Source