Hydrochloric Acid → HCID 57717588, compound

HRID 2283820Notes

Reaction equation

HRID 2283820 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C:6]([CH3:26])([CH3:25])[CH2:7][C:8]1[N:9]([CH2:22][CH2:23][CH3:24])[N:10]=[C:11]2[C:20]=1[C:19]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N:13]=[C:12]2[NH2:21].C(N(CC)CC)C.Cl>ClCCl.CO>[NH2:21][C:12]1[C:11]2=[N:10][N:9]([CH2:22][CH2:23][CH3:24])[C:8]([CH2:7][C:6]([NH:5][C:1](=[O:3])[CH3:2])([CH3:26])[CH3:25])=[C:20]2[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 57717565HCID 57717565, compound

Product 1

HCID 57717588HCID 57717588, compoundYield 72.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (221 μL, 3.14 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, 840 mg, 2.82 mmol) and triethylamine (591 μL, 4.24 mmol) in dichloromethane (25.2 mL). The solution was stirred for 20.5 h at ambient temperature, then was concentrated under reduced pressure to yield a foam that was dissolved in methanol. To the solution was added concentrated hydrochloric acid (2 mL). The solution was stirred at ambient temperature for 90 minutes, then heated at reflux for 40 minutes. After cooling to ambient temperature, the solution was concentrated under reduced pressure and 2 M aqueous sodium carbonate was added until the pH was basic. The solution was extracted with chloroform. The organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL), then triethylamine (786 mL) and acetyl chloride (300 mL) were added. The reaction was worked up as before, then methanol (20 mL) and concentrated hydrochloric acid (2 mL) were added. The solution was heated at reflux for 30 minutes, left to stand at ambient temperature overnight, then heated at reflux again for 30 minutes. After cooling to ambient temperature, the solution was concentrated under reduced pressure and 2M aqueous sodium carbonate was added until the pH was adjusted to pH 10-11. The solution was extracted with chloroform three times. The organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified twice by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 20-30% CMA in chloroform for the first column; gradient elution with 4-10% methanol in chloroform for the second column). The appropriate fractions were combined and concentrated under reduced pressure to yield a colorless foam that was crystallized from ethyl acetate/hexanes. A white solid was isolated and dried under vacuum at elevated temperature to yield 698 mg of N-[2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)-1,1-dimethylethyl]acetamide as a white solid, mp 182-183° C.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customto yield a foam that
  3. stirringThe solution was stirred at ambient temperature for 90 minutes
  4. temperatureheated
  5. temperatureat reflux for 40 minutes
  6. temperatureAfter cooling to ambient temperature
  7. concentrationthe solution was concentrated under reduced pressure and 2 M aqueous sodium carbonate
  8. additionwas added until the pH
  9. extractionThe solution was extracted with chloroform
  10. dry with materialThe organic layers were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  14. additiontriethylamine (786 mL) and acetyl chloride (300 mL) were added
  15. additionwere added
  16. temperatureThe solution was heated
  17. temperatureat reflux for 30 minutes
  18. waitleft
  19. waitto stand at ambient temperature overnight
  20. temperatureheated
  21. temperatureat reflux again for 30 minutes
  22. temperatureAfter cooling to ambient temperature
  23. concentrationthe solution was concentrated under reduced pressure and 2M aqueous sodium carbonate
  24. additionwas added until the pH
  25. extractionThe solution was extracted with chloroform three times
  26. dry with materialThe organic layers were dried over sodium sulfate
  27. filtrationfiltered
  28. concentrationconcentrated under reduced pressure
  29. customThe crude product was purified twice by chromatography on a HORIZON HPFC system (
  30. washsilica gel, gradient elution with 20-30% CMA in chloroform for the first column
  31. washgradient elution with 4-10% methanol in chloroform for the second column)
  32. concentrationconcentrated under reduced pressure
  33. customto yield a colorless foam that
  34. customwas crystallized from ethyl acetate/hexanes
  35. customA white solid was isolated
  36. customdried under vacuum at elevated temperature

Sources & evidence

ORD record
ord-334734a673f4455687f8d16bd4e1800f
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

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