반응 #73054

반응 방정식

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

수율 88.3%

용매

dichloromethane

반응 조건

후처리

1. 1
   온도to 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
   농축The reaction mixture was concentrated under reduced pressure
5. 5
   기타The residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
6. 6
   세척The organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
7. 7
   건조dried over sodium sulfate
8. 8
   여과filtered
9. 9
   농축concentrated under reduced pressure
10. 10
    기타to provide an off white solid
11. 11
    기타This material was triturated with acetonitrile
12. 12
    기타recrystallized from chloroform/hexanes
13. 13
    기타isolated by filtration
14. 14
    세척washed with hexanes
15. 15
    기타dried under high vacuum at 130° C.

실험 절차

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.

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