Methanol → HCID 57657241, compound

HRID 244855Notes

Reaction equation

HRID 244855 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][O:30][CH2:29][CH2:28]3)=[O:26])=[CH:5][C:4]=2[N:3]=1.CO>C(Cl)(Cl)Cl>[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][O:30][CH2:29][CH2:28]3)=[O:26])=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 57657229HCID 57657229, compound

Product 1

HCID 57657241HCID 57657241, compoundYield 10.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A stirring solution of 1-[4-amino-2-(methoxymethyl)-7-(3-morpholin-4-yl-3-oxopropyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (460 mg, 1.04 mmol) in chloroform (120 mL) was sealed with a septum and purged with nitrogen gas. The solution was cooled in an ice water bath and a solution of 1.0 M boron tribromide in dichloromethane (6.6 mL) was added via syringe. The reaction was stirred for 18 hours while warming to ambient temperature. In order to complete the reaction three additional portions (3 mL, 10 mL, and 10 mL) of 1.0 M boron tribromide in dichloromethane were added at approximately 18 hour intervals. Methanol (75 mL) was added. The reaction was concentrated to a dark purple liquid and then stirred in 10% aqueous hydrochloric acid (100 mL) for three days. Solid sodium carbonate was slowly added until the pH equaled 10. The solution was concentrated to a white solid. The solid was washed with methanol (2×100 mL) and filtered. The filtrate was absorbed onto silica (2 tbsp) and then purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-20% CMA over 1400 mL, followed by 20-30% CMA over 1600 mL) to provide 48 mg of 1-[4-amino-2-(hydroxymethyl)-7-(3-morpholin-4-yl-3-oxopropyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white crystalline solid, mp 223-225° C.

Workup

  1. custompurged with nitrogen gas
  2. temperatureThe solution was cooled in an ice water bath
  3. additiona solution of 1.0 M boron tribromide in dichloromethane (6.6 mL) was added via syringe
  4. customthe reaction three additional portions (3 mL, 10 mL, and 10 mL) of 1.0 M boron tribromide in dichloromethane
  5. additionwere added at approximately 18 hour intervals
  6. concentrationThe reaction was concentrated to a dark purple liquid
  7. stirringstirred in 10% aqueous hydrochloric acid (100 mL) for three days
  8. additionSolid sodium carbonate was slowly added until the pH
  9. concentrationThe solution was concentrated to a white solid
  10. washThe solid was washed with methanol (2×100 mL)
  11. filtrationfiltered
  12. customThe filtrate was absorbed onto silica (2 tbsp)
  13. custompurified by chromatography
  14. washeluting with a CMA

Sources & evidence

ORD record
ord-a16346cc86f44e7aa5c0b0943dad72bd
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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