Triethylamine → HCID 57717499, compound

HRID 1984423Notes

Reaction equation

HRID 1984423 reaction equation
[CH:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:10][C:11]([CH3:31])([CH3:30])[CH2:12][C:13]1[N:14]([CH2:27][CH2:28][CH3:29])[N:15]=[C:16]2[C:25]=1[C:24]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:18]=[C:17]2[NH2:26].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[NH2:26][C:17]1[C:16]2=[N:15][N:14]([CH2:27][CH2:28][CH3:29])[C:13]([CH2:12][C:11]([NH:10][C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:8])([CH3:31])[CH3:30])=[C:25]2[C:24]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N:18]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 75938Cyclohexanecarbonyl chloride2×HCID 57717565HCID 57717565, compound

Product 1

HCID 57717499HCID 57717499, compoundYield 73.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cyclohexanecarbonyl chloride (401 μL, 3.00 mmol) was added to a 0° C. stirred solution of 1-(2-amino-2-methylpropyl)-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-amine (prepared as described in Example 64, 892 mg, 3.00 mmol) and triethylamine (627 μL, 4.5 mmol) in dichloromethane (26.7 mL). After 3 hours at 0° C., the solution was stirred for 2 days at ambient temperature. More triethylamine (697 μL) and cyclohexanecarbonyl chloride (602 μL) was added. After 30 minutes, 2 M aqueous sodium carbonate was added to the solution. The mixture was extracted with chloroform four times. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Methanol (20 mL) and concentrated hydrochloric acid (2 mL) were added. The solution was heated at reflux for 4 hours, then left to stand at ambient temperature overnight, then heated at reflux again for brief periods of time during the next 2 days. In all, the solution was heated at reflux for a total of 7 hours. After cooling to ambient temperature, 2 M aqueous sodium carbonate was added to adjust the mixture to pH 10-11. The mixture was concentrated under reduced pressure to remove the methanol. Water was added and a solid was isolated from the mixture by filtration. The solid was washed with water. Chloroform was added to the solid, and the mixture was filtered. The filtrate was concentrated under reduced pressure and purified by IFC. The appropriate fractions were combined and concentrated to a white solid that was recrystallized from 50% ethyl acetate/hexanes. The crystals were isolated by filtration and dried to yield 896 mg of N-[2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)-1,1-dimethylethyl]cyclohexanecarboxamide as a white solid, mp 190-191° C.

Workup

  1. waitAfter 30 minutes
  2. extractionThe mixture was extracted with chloroform four times
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. additionMethanol (20 mL) and concentrated hydrochloric acid (2 mL) were added
  7. temperatureThe solution was heated
  8. temperatureat reflux for 4 hours
  9. waitleft
  10. waitto stand at ambient temperature overnight
  11. temperatureheated
  12. temperatureat reflux again for brief periods of time during the next 2 days
  13. temperatureIn all, the solution was heated
  14. temperatureat reflux for a total of 7 hours
  15. temperatureAfter cooling to ambient temperature
  16. addition2 M aqueous sodium carbonate was added
  17. concentrationThe mixture was concentrated under reduced pressure
  18. customto remove the methanol
  19. additionWater was added
  20. customa solid was isolated from the mixture by filtration
  21. washThe solid was washed with water
  22. additionChloroform was added to the solid
  23. filtrationthe mixture was filtered
  24. concentrationThe filtrate was concentrated under reduced pressure
  25. custompurified by IFC
  26. concentrationconcentrated to a white solid
  27. customthat was recrystallized from 50% ethyl acetate/hexanes
  28. customThe crystals were isolated by filtration
  29. customdried

Sources & evidence

ORD record
ord-268f218af05e4ba49c026d3aad8d634c
Source dataset
uspto-grants-2009_06
Patent number
US07544697B2

Reaction notes

Loading…