HCID 57657224, compound → HCID 57657230, compound

HRID 244854Notes

Reaction equation

HRID 244854 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21]C)[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([N:27]([CH3:29])[CH3:28])=[O:26])=[CH:5][C:4]=2[N:3]=1>ClCCl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][OH:21])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([N:27]([CH3:28])[CH3:29])=[O:26])=[CH:5][C:4]=2[N:3]=1

Participants

3

Reactant 1

HCID 57657224HCID 57657224, compound

Product 1

HCID 57657230HCID 57657230, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirring solution of 3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide (523 mg, 1.31 mmol) in dichloromethane (125 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 (6.6 mL) was added via syringe. The resulting mixture was stirred for 18 hours while warming to ambient temperature. Methanol (50 mL) was added and the mixture was concentrated under reduced pressure. The resulting solid was dissolved in a 2.0 M solution of ammonia in methanol (75 mL) and the solution was concentrated under reduced pressure to yield a solid. This step was repeated two more times with silica gel (1 tbsp) being added prior to the final concentration. The sample absorbed on silica was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-25% CMA over 1200 mL, followed by 25-40% CMA over 1300 mL) to provide 298 mg of 3-[4-Amino-2-(hydroxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide as a white crystalline solid, mp 228-230° 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 (6.6 mL) was added via syringe
  4. additionMethanol (50 mL) was added
  5. concentrationthe mixture was concentrated under reduced pressure
  6. dissolutionThe resulting solid was dissolved in a 2.0 M solution of ammonia in methanol (75 mL)
  7. concentrationthe solution was concentrated under reduced pressure
  8. customto yield a solid
  9. additionbeing added
  10. concentrationto the final concentration
  11. customThe sample absorbed on silica
  12. customwas purified by chromatography
  13. washeluting with a CMA

Sources & evidence

ORD record
ord-f9c6b088c39243c88be2ce8ab19ac016
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

Loading…