Triethylamine → tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamate

HRID 598363Notes

Reaction equation

HRID 598363 reaction equation
[CH2:1]([O:3][CH2:4][C:5](Cl)=O)[CH3:2].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[CH3:22])=[CH:16][CH:15]=[C:14]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:13]=2.C(N(CC)CC)C>ClCCl>[CH2:33]([O:32][C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:19]([CH2:20][C:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[CH3:22])[C:5]([CH2:4][O:3][CH2:1][CH3:2])=[N:8][C:9]=3[CH:10]=[N:11][C:12]=2[CH:13]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 86626172Tert-butyl [2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate

Product 1

HCID 86626174tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamateYield 72.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethoxyacetyl chloride (1.82 mL, 16.60 mmol) was added to a chilled (0° C.) solution of tert-butyl [2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate (6.04 g, 13.8 mmol) and triethylamine (3.86 mL, 27.68 mmol) in 150 mL of anhydrous dichloromethane. After stirring for 30 minutes, the cooling bath was removed and the reaction was stirred for 24 hours at ambient temperature. The volatiles were removed under reduced pressure and the resulting residue was dissolved in ethanol, followed by the addition of 3.86 mL of trietylamine. The reaction was heated at reflux for 2.5 days and then cooled to ambient temperature. The solvent was removed under reduced pressure and dichloromethane was added. The solution was sequentially washed with aqueous sodium bicarbonate followed by brine; dried over sodium sulfate; filtered; and concentrated under reduced pressure. The residue was purified using flash column chromatography on silica gel, eluting with 5% methanol in dichloromethane. Clean fractions were concentrated; while fractions containing both the product and the starting material were resubmitted to the reaction conditions and repurified as described above. The combined lots provided a total of 5.07 g of tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamate was obtained as an orange foam.

Workup

  1. customthe cooling bath was removed
  2. stirringthe reaction was stirred for 24 hours at ambient temperature
  3. customThe volatiles were removed under reduced pressure
  4. dissolutionthe resulting residue was dissolved in ethanol
  5. additionfollowed by the addition of 3.86 mL of trietylamine
  6. temperatureThe reaction was heated
  7. temperatureat reflux for 2.5 days
  8. customThe solvent was removed under reduced pressure and dichloromethane
  9. additionwas added
  10. washThe solution was sequentially washed with aqueous sodium bicarbonate
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationand concentrated under reduced pressure
  14. customThe residue was purified
  15. washeluting with 5% methanol in dichloromethane
  16. concentrationwere concentrated
  17. additionwhile fractions containing both the product
  18. customthe starting material were resubmitted to the reaction conditions
  19. customrepurified

Sources & evidence

ORD record
ord-1a6d800ca54a4774a81096d47f44ef9b
Source dataset
uspto-grants-2011_03
Patent number
US07897597B2

Reaction notes

Loading…