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

HRID 44776

Reaction equation

HRID 44776 reaction equation
C(N(CC)CC)C.Cl.Cl.[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:32][CH3:33])[N:23]([CH2:24][C:25]3([OH:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:19]=2[C:18]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1.[N:34]1([C:40](Cl)=[O:41])[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>ClCCl>[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:32][CH3:33])[N:23]([CH2:24][C:25]3([OH:31])[CH2:30][CH2:29][N:28]([C:40]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)=[O:41])[CH2:27][CH2:26]3)[C:19]=2[C:18]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 848104-Morpholinecarbonyl chloride2×HCID 575155314-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]piperidin-4-ol dihydrochloride

Product 1

HCID 575155324-[(4-amino-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]-1-(morpholin-4-ylcarbonyl)piperidin-4-olYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

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.

Workup

  1. temperatureto slowly warm to ambient temperature
  2. waitat 30° C. for 2 days
  3. stirringthe reaction mixture was stirred at 30° C. for 5 days
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customThe residue was partitioned between chloroform (150 mL) and saturated aqueous sodium carbonate (30 mL)
  6. washThe organic was washed with saturated aqueous sodium carbonate (20 mL) and brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto provide an off white solid
  11. customThis material was triturated with acetonitrile
  12. customrecrystallized from chloroform/hexanes
  13. customisolated by filtration
  14. washwashed with hexanes
  15. customdried under high vacuum at 130° C.

Sources & evidence

ORD record
ord-314919e7a4ec4297bd513cff458cb468
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Linked notes

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