Dichloromethane → HCID 58833687, compound

HRID 2203574Notes

Reaction equation

HRID 2203574 reaction equation
B(Br)(Br)Br.ClCCl.[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:25][CH2:26][O:27]C)[N:21]([CH2:22][CH2:23][CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([O:29][CH2:30][CH2:31][CH2:32][NH:33][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:12][C:11]=2[N:10]=1>>[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:25][CH2:26][OH:27])[N:21]([CH2:22][CH2:23][CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([O:29][CH2:30][CH2:31][CH2:32][NH:33][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:12][C:11]=2[N:10]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 25134Boron tribromide2×HCID 68971706HCID 68971706, compound

Product 1

HCID 58833687HCID 58833687, compoundYield 30.8%

Conditions

Temperature
0 °C

Procedure

A 1.0 M solution of boron tribromide in dichloromethane (2.55 mL, 2.55 mmol) was added over 1 minute to a slurry of N-(3-{[4-amino-2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-yl]oxy}propyl)-2-methylpropanamide (1.09 g, 2.55 mmol) at 0° C. The clumpy slurry was allowed to stir for 15 minutes at 0° C., then was allowed to stir for another hour at ambient temperature. Additional boron tribromide solution (0.6 mL, 0.6 mmol) was added. After 16 hours, the reaction was quenched with 6 M hydrochloric acid (10 mL), stirred until all the solids dissolved, and the dichloromethane was removed under reduced pressure. The aqueous layer was adjusted to approximately pH 13 with 50% aqueous sodium hydroxide and was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and evaporated. The material was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 2-22% CMA in chloroform) followed by trituration with acetonitrile to afford 0.325 g of N-(3-{[4-amino-2-(2-hydroxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-yl]oxy}propyl)-2-methylpropanamide as a white solid, mp 190.5-192° C.

Workup

  1. stirringto stir for another hour at ambient temperature
  2. waitAfter 16 hours
  3. customthe reaction was quenched with 6 M hydrochloric acid (10 mL)
  4. stirringstirred until all the solids
  5. dissolutiondissolved
  6. customthe dichloromethane was removed under reduced pressure
  7. extractionwas extracted with ethyl acetate
  8. washThe organic layer was washed with water and saturated aqueous sodium chloride
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe material was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 2-22% CMA in chloroform)

Sources & evidence

ORD record
ord-0938ae6051b0406c8fa24403aa054bef
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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