تفاعل #73054

معادلة التفاعل

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

المردود 88.3%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto 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
   تركيزThe reaction mixture was concentrated under reduced pressure
5. 5
   أخرىThe residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
6. 6
   غسيلThe organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
7. 7
   تجفيفdried over sodium sulfate
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated under reduced pressure
10. 10
    أخرىto provide an off white solid
11. 11
    أخرىThis material was triturated with acetonitrile
12. 12
    أخرىrecrystallized from chloroform/hexanes
13. 13
    أخرىisolated by filtration
14. 14
    غسيلwashed with hexanes
15. 15
    أخرىdried under high vacuum at 130° C.

الإجراء التجريبي

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.

المصدر