Реакция #73054

Уравнение реакции

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

Выход 88.3%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   Температураto 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
   КонцентрированиеThe reaction mixture was concentrated under reduced pressure
5. 5
   ДругоеThe residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
6. 6
   ПромывкаThe organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
7. 7
   Сушкаdried over sodium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated under reduced pressure
10. 10
    Другоеto provide an off white solid
11. 11
    ДругоеThis material was triturated with acetonitrile
12. 12
    Другоеrecrystallized from chloroform/hexanes
13. 13
    Другоеisolated by filtration
14. 14
    Промывкаwashed with hexanes
15. 15
    Другоеdried under high vacuum at 130° C.

Методика

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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