Boron tribromide → HCID 57555834, compound

HRID 81919Notes

Reaction equation

HRID 81919 reaction equation
B(Br)(Br)Br.[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([CH2:31][O:32]CC)[N:18]([CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:25])[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1>ClCCl>[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([CH2:31][OH:32])[N:18]([CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:25])[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 67519463HCID 67519463, compound

Product 1

HCID 57555834HCID 57555834, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boron tribromide (2.5 equivalents, 14.6 mL of 1 M solution in dichloromethane) was added dropwise to a cooled (ice bath) suspension of N-{4-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}cyclopentanecarboxamide (2.4 g, 5.8 mmol) in dichloromethane (25 mL). The reaction mixture was allowed to slowly warm to ambient temperature and then stirred for 6 days. Additional boron tribromide (5 equivalents, 29 mmol, 29 mL) was added and the reaction was stirred at ambient until starting material was consumed. The reaction was quenched slowly with methanol (100 mL) and then concentrated under reduced pressure. The residue was combined with 6 M hydrochloric acid (100 mL), heated to 50° C., and stirred for 2 hours. The resulting solution was cooled (ice bath) and then free-based (pH 9) with the addition of 6 M aqueous sodium hydroxide. A brown gummy solid formed in the basic aqueous solution. The aqueous liquid was decanted from the solid and acetonitrile was added (30 mL). A white precipitate formed and was isolated by filtration. The white precipitate was then triturated with hot acetonitrile, allowed to cool, isolated by filtration, washed with ether, and dried under vacuum to provide N-{4-[4-amino-2-(hydroxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}cyclopentanecarboxamide (0.48 g) as a fine white solid, mp 183-186° C.; MS (ESI) m/z 382 (M+H)+; Anal. Calcd for C21H27N5O2: C, 65.35; H, 7.18; N, 18.14. Found C, 65.06; H, 6.90; N, 18.13.

Workup

  1. temperaturea cooled
  2. stirringthe reaction was stirred at ambient
  3. customwas consumed
  4. customThe reaction was quenched slowly with methanol (100 mL)
  5. concentrationconcentrated under reduced pressure
  6. temperatureheated to 50° C.
  7. stirringstirred for 2 hours
  8. temperatureThe resulting solution was cooled (ice bath)
  9. additionfree-based (pH 9) with the addition of 6 M aqueous sodium hydroxide
  10. customA brown gummy solid formed in the basic aqueous solution
  11. customThe aqueous liquid was decanted from the solid and acetonitrile
  12. additionwas added (30 mL)
  13. customA white precipitate formed
  14. customwas isolated by filtration
  15. customThe white precipitate was then triturated with hot acetonitrile
  16. temperatureto cool
  17. customisolated by filtration
  18. washwashed with ether
  19. customdried under vacuum

Sources & evidence

ORD record
ord-651b5868c20240708df2d9978444fd9f
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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