Hydrochloric Acid → HCID 57717515, compound

HRID 2283824Notes

Reaction equation

HRID 2283824 reaction equation
[CH3:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[NH2:7][C:8]([CH3:28])([CH3:27])[CH2:9][C:10]1[N:11]([CH2:24][CH2:25][CH3:26])[N:12]=[C:13]2[C:22]=1[C:21]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:15]=[C:14]2[NH2:23].C(N(CC)CC)C.Cl.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.CO>[NH2:23][C:14]1[C:13]2=[N:12][N:11]([CH2:24][CH2:25][CH3:26])[C:10]([CH2:9][C:8]([NH:7][C:3](=[O:4])[CH:2]([CH3:6])[CH3:1])([CH3:28])[CH3:27])=[C:22]2[C:21]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 62325Isobutyryl chlorideHCID 57717565HCID 57717565, compound

Product 1

HCID 57717515HCID 57717515, compoundYield 73.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2-Methylpropanoyl chloride (786 μL, 7.50 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 (1.32 mL, 9.5 mmol) in dichloromethane (26.7 mL). After 10 minutes at 0° C., the solution was stirred for 2 hours at ambient temperature. The solution was concentrated to afford a white solid that was dissolved in methanol (20 mL) and concentrated hydrochloric acid (4 mL). The solution was heated at reflux for 3.5 hours, then was left to stand at ambient temperature overnight. To the solution was added 2 M aqueous sodium carbonate until the pH was basic. The mixture was concentrated under reduced pressure to remove the methanol. The mixture was extracted with chloroform four times. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to yield an off-white solid that was purified by IFC (silica gel, eluted with CMA in chloroform). The appropriate fractions were combined and concentrated under reduced pressure to yield a white foam that was crystallized from 50% ethyl acetate in hexanes. The solid was isolated by filtration, washed with 50% ethyl acetate in hexanes, and dried to yield 815 mg of N-[2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)-1,1-dimethylethyl]-2-methylpropanamide as a white solid, mp 177-178.5° C.

Workup

  1. concentrationThe solution was concentrated
  2. customto afford a white solid
  3. temperatureThe solution was heated
  4. temperatureat reflux for 3.5 hours
  5. waitwas left
  6. waitto stand at ambient temperature overnight
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customto remove the methanol
  9. extractionThe mixture was extracted with chloroform four times
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto yield an off-white solid
  14. customthat was purified by IFC (silica gel, eluted with CMA in chloroform)
  15. concentrationconcentrated under reduced pressure
  16. customto yield a white foam that
  17. customwas crystallized from 50% ethyl acetate in hexanes
  18. customThe solid was isolated by filtration
  19. washwashed with 50% ethyl acetate in hexanes
  20. customdried

Sources & evidence

ORD record
ord-ef1f29dee0d446708e5016d9ca126c3b
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

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