HCID 57657232, compound → HCID 57657234, compound

HRID 244859Notes

Reaction equation

HRID 244859 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][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[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][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:5][C:4]=2[N:3]=1

Participants

3

Reactant 1

HCID 57657232HCID 57657232, compound

Product 1

HCID 57657234HCID 57657234, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-{3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]propyl}methanesulfonamide (630 mg, 1.45 mmol) in dichloromethane (125 mL) was sealed with a septum and purged with nitrogen gas. A 1.0 M solution of boron tribromide in dichloromethane (7.3 mL) was added via syringe. The resulting mixture was stirred for 18 hours. Methanol (50 mL) was added and the solution was concentrated under reduced pressure. The resulting solid was dissolved in a 2.0 M solution of ammonia in methanol (75 mL) and then concentrated under reduced pressure. This step was repeated two more times with silica gel (1 tbsp) being added prior to final concentration. The crude product absorbed on silica was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with CMA:chloroform gradient; 0-25% CMA over 1200 mL, followed by 25-40% CMA over 1900 mL). The solid product was washed with water, filtered, and dried to provide 325 mg of N-{3-[4-amino-2-(hydroxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]propyl}methanesulfonamide as a white solid, mp 202-205° C.

Workup

  1. custompurged with nitrogen gas
  2. additionA 1.0 M solution of boron tribromide in dichloromethane (7.3 mL) was added via syringe
  3. additionMethanol (50 mL) was added
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe resulting solid was dissolved in a 2.0 M solution of ammonia in methanol (75 mL)
  6. concentrationconcentrated under reduced pressure
  7. additionbeing added
  8. concentrationto final concentration
  9. customThe crude product absorbed on silica
  10. customwas purified by chromatography
  11. washa HORIZON HPFC system (silica cartridge, eluting with CMA:chloroform gradient; 0-25% CMA over 1200 mL, followed by 25-40% CMA over 1900 mL)
  12. washThe solid product was washed with water
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-4a35b996a01d48c59febcd2b0615ccaa
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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