Hydrochloric Acid → HCID 58869084, compound

HRID 1623147Notes

Reaction equation

HRID 1623147 reaction equation
Cl.O1CCOCC1.[NH2:8][C:9]1[C:14]2[N:15]=[C:16]([CH2:38][CH2:39][CH3:40])[N:17]([CH2:18][CH2:19][CH2:20][CH2:21][N:22]([O:30]C(OC(C)(C)C)=O)[C:23](=[O:29])OC(C)(C)C)[C:13]=2[C:12]([CH3:41])=[C:11]([CH3:42])[N:10]=1.C(N(CC)CC)C.[C:50]1([N:56]=C=O)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>ClCCl.C(=O)(O)[O-].[Na+].CO>[NH2:8][C:9]1[C:14]2[N:15]=[C:16]([CH2:38][CH2:39][CH3:40])[N:17]([CH2:18][CH2:19][CH2:20][CH2:21][N:22]([OH:30])[C:23]([NH:56][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:29])[C:13]=2[C:12]([CH3:41])=[C:11]([CH3:42])[N:10]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 86612256HCID 86612256, compound

Product 1

HCID 58869084HCID 58869084, compoundYield 28.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 4N hydrochloric acid in dioxane (2.5 mL, 10.2 mmol, 20 eq) was added to a solution of tert-butyl 4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl[(tert-butoxycarbonyl)oxy]carbamate (250 mg, 0.51 mmol), prepared as described in Parts A-F of Example 14, and stirred for 1 hour at ambient temperature. Methanol (2 mL) was added to the reaction mixture, which was stirred overnight. The reaction mixture was concentrated under reduced pressure and the material was concentrated from methanol and chloroform and dried. The material was suspended in dichloromethane (5 mL) and triethylamine (0.71 mL, 5.1 mmol) and cooled to −5° C. Phenyl isocyanate (0.056 mL, 0.51 mmol) was added dropwise and the reaction mixture was slowly allowed to warm to ambient temperature. After two hours, the reaction mixture was diluted with dichloromethane (10 mL) and saturated aqueous sodium bicarbonate (5 mL) and stirred vigorously and the phases were separated. The aqueous layer was extracted with dichloromethane (2×10 mL) and the combined organics were washed with saturated aqueous sodium bicarbonate (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to produce a white solid. The material was purified by HPFC (eluting with 5-30% CMA in chloroform), recrystallized from acetonitrile, triturated with ethyl acetate and dried at 80° C. under high vacuum to afford 60 mg of 1-[4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridine-1-yl)butyl]-1-hydroxy-3-phenyl-urea as a white powder, mp 159.0-160.5° C. Anal. Calcd for C22H30N6O2 C, 64.37; H, 7.37; N, 20.47. Found: C, 64.01; H, 7.20; N, 20.27.

Workup

  1. customprepared
  2. stirringwas stirred overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. concentrationthe material was concentrated from methanol and chloroform
  5. customdried
  6. temperatureto warm to ambient temperature
  7. waitAfter two hours
  8. stirringstirred vigorously
  9. customthe phases were separated
  10. extractionThe aqueous layer was extracted with dichloromethane (2×10 mL)
  11. washthe combined organics were washed with saturated aqueous sodium bicarbonate (10 mL)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customto produce a white solid
  16. customThe material was purified by HPFC (eluting with 5-30% CMA in chloroform)
  17. customrecrystallized from acetonitrile
  18. customtriturated with ethyl acetate
  19. customdried at 80° C. under high vacuum

Sources & evidence

ORD record
ord-51d75c8dd02e4e118bd7faa6266fb38c
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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