Acetic Anhydride → HCID 57657239, compound

HRID 244858Notes

Reaction equation

HRID 244858 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH3:22])[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][CH2:25][NH2:26])=[CH:5][C:4]=2[N:3]=1.C(N(CC)CC)C.[C:34](OC(=O)C)(=[O:36])[CH3:35]>>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH3:22])[N:14]([CH2:15][C:16]([OH:18])([CH3:17])[CH3:19])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][CH2:25][NH:26][C:34](=[O:36])[CH3:35])=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 69082296HCID 69082296, compound

Product 1

HCID 57657239HCID 57657239, compoundYield 41.3%

Procedure

A solution of 1-[4-amino-7-(3-aminopropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (1.25 g, 3.50 mmol) in triethylamine (2.4 mL, 17.5 mmol) was cooled to 0° C. in an ice water bath and acetic anhydride (393 mg, 3.85 mmol) was added. The solution was stirred for approximately 18 hours while warming to ambient temperature. The solution was concentrated under reduced pressure and the residue was partitioned between 1% aqueous sodium carbonate (125 mL) and chloroform (50 mL). Successive chloroform extractions were performed until no product was present in the aqueous layer. The combined organic fractions were concentrated under reduced pressure and dissolved in methanol (100 mL). To this solution was added solid potassium carbonate (3 tsp) and the reaction was heated to reflux temperature for 2 hours. After cooling to ambient temperature, the mixture was filtered, concentrated and partitioned between water (50 mL) and chloroform (50 mL). Crude product was extracted from the aqueous fraction through successive chloroform extractions until no product remained in the aqueous layer. The combined organic extracts were concentrated and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-30% CMA over 1500 mL, followed by 30% CMA over 1000 mL) to provide 578 mg of N-{3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]propyl}acetamide as a white semi-solid.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. customthe residue was partitioned between 1% aqueous sodium carbonate (125 mL) and chloroform (50 mL)
  3. extractionSuccessive chloroform extractions
  4. concentrationThe combined organic fractions were concentrated under reduced pressure
  5. dissolutiondissolved in methanol (100 mL)
  6. additionTo this solution was added solid potassium carbonate (3 tsp)
  7. temperaturethe reaction was heated
  8. temperatureto reflux temperature for 2 hours
  9. temperatureAfter cooling to ambient temperature
  10. filtrationthe mixture was filtered
  11. concentrationconcentrated
  12. custompartitioned between water (50 mL) and chloroform (50 mL)
  13. extractionCrude product was extracted from the aqueous fraction through successive chloroform extractions until no product
  14. concentrationThe combined organic extracts were concentrated
  15. custompurified by chromatography
  16. washeluting with a CMA

Sources & evidence

ORD record
ord-974c1f6eee9c4f6888ce24cf336091ef
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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