HCID 57657244, compound → HCID 57657267, compound

HRID 244857Notes

Reaction equation

HRID 244857 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]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([N:27]3[CH2:32][CH2:31][S:30](=[O:34])(=[O:33])[CH2:29][CH2:28]3)=[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]([CH3:17])([OH:18])[CH3:19])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([N:27]3[CH2:32][CH2:31][S:30](=[O:34])(=[O:33])[CH2:29][CH2:28]3)=[O:26])=[CH:5][C:4]=2[N:3]=1

Participants

3

Reactant 1

HCID 57657244HCID 57657244, compound

Product 1

HCID 57657267HCID 57657267, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 1-[4-amino-7-[3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl]-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (655 mg, 1.34 mmol) in dichloromethane (125 mL), sealed with a septum and purged with nitrogen gas, was added a 1.0 M solution of boron tribromide in dichloromethane (6.6 mL) 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 to a solid. This step was repeated two more times with silica gel (1 tbsp) being added prior to the final concentration. The crude product 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). The recovered solid was washed with 1% aqueous sodium carbonate and filtered to provide 325 mg of 1-[4-amino-7-[3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl]-2-(hydroxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an off white semi-solid.

Workup

  1. custompurged with nitrogen gas
  2. additionwas added a 1.0 M solution of boron tribromide in dichloromethane (6.6 mL) 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 to a solid
  7. additionbeing added
  8. concentrationto the final concentration
  9. customThe crude product absorbed on silica
  10. customwas purified by chromatography
  11. washeluting with a CMA
  12. washThe recovered solid was washed with 1% aqueous sodium carbonate
  13. filtrationfiltered

Sources & evidence

ORD record
ord-894b2d60c6bf4cffa56bf0b37bd49f70
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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