HCID 11152911, compound → HCID 57555838, compound

HRID 1925465Notes

Reaction equation

HRID 1925465 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][O:25]CC)[N:14]([CH2:15][CH2:16][NH:17][C:18]([NH:20][CH:21]([CH3:23])[CH3:22])=[O:19])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1>ClCCl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][OH:25])[N:14]([CH2:15][CH2:16][NH:17][C:18]([NH:20][CH:21]([CH3:23])[CH3:22])=[O:19])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

3

Reactant 1

HCID 11152911HCID 11152911, compound

Product 1

HCID 57555838HCID 57555838, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirring solution of N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}-N′-isopropylurea (400 mg, 1.1 mmol) in dichloromethane (50 mL) was sealed with a septum and purged with nitrogen gas. The solution was cooled in an ice/water bath and a 1.0 M solution of boron tribromide in dichloromethane (2.2 mL) was added via syringe. The resulting mixture was stirred for 2 hours while warming to ambient temperature. The mixture was cooled back to 0° C. in an ice/water bath and the second portion of boron tribromide (1.0 M, 5.5 mL) was added. The reaction was stirred for 18 hours while warming to ambient temperature. Aqueous hydrochloric acid (6N, 10 ml) was added and the mixture was stirred for 1 hour. The layers were separated and the aqueous fraction was neutralized by the slow addition of solid sodium hydroxide until the pH reached 14. A fine precipitate formed. The aqueous mixture was extracted with chloroform (2×50 mL) and filtered. The resulting solid (filter cake) was combined with the organic extracts, methanol (50 mL), and silica gel (5 g). The mixture was concentrated under reduced pressure. The crude product absorbed on silica was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-35% CMA in chloroform over 2.6 L) followed by recrystallization from acetonitrile to provide 170 mg of N-{2-[4-amino-2-(hydroxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}-N′-isopropylurea as an off-white solid, mp>240° C.

Workup

  1. custompurged with nitrogen gas
  2. temperatureThe solution was cooled in an ice/water bath
  3. additiona 1.0 M solution of boron tribromide in dichloromethane (2.2 mL) was added via syringe
  4. temperatureThe mixture was cooled back to 0° C. in an ice/water bath
  5. additionthe second portion of boron tribromide (1.0 M, 5.5 mL) was added
  6. stirringThe reaction was stirred for 18 hours
  7. temperaturewhile warming to ambient temperature
  8. additionAqueous hydrochloric acid (6N, 10 ml) was added
  9. stirringthe mixture was stirred for 1 hour
  10. customThe layers were separated
  11. additionthe aqueous fraction was neutralized by the slow addition of solid sodium hydroxide until the pH
  12. customA fine precipitate formed
  13. extractionThe aqueous mixture was extracted with chloroform (2×50 mL)
  14. filtrationfiltered
  15. filtrationThe resulting solid (filter cake)
  16. concentrationThe mixture was concentrated under reduced pressure
  17. customThe crude product absorbed on silica
  18. customwas purified by chromatography
  19. washa HORIZON HPFC system (silica cartridge, eluting with 0-35% CMA in chloroform over 2.6 L)
  20. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-a220a39c003e47268a8471724dcd9b62
Source dataset
uspto-grants-2012_05
Patent number
US08178677B2

Reaction notes

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