Triethylamine → HCID 16224282, compound

HRID 1930098Notes

Reaction equation

HRID 1930098 reaction equation
C(N(CC)CC)C.[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:31][CH3:32])[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:17]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35]>CN(C)C=O>[CH2:31]([C:20]1[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:17]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([NH:8][C:34](=[O:35])[O:36][CH2:37][CH3:38])[C:18]=2[N:19]=1)[CH3:32]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 10928Ethyl chloroformate2×HCID 10309114CPG-52852

Product 1

HCID 16224282HCID 16224282, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Triethylamine (3.86 mL, 10 eq) was added to a chilled (ice/water bath) suspension of N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide (1.0 g, 1 eq) in N,N-dimethylformamide (DMF) (10 mL). Ethyl chloroformate (1.5 g, 5 eq) was added dropwise to give a clear solution. The reaction mixture was allowed to come to ambient temperature with stirring for 2 hours. Additional triethylamine (3.86 mL, 10 eq) and ethyl chloroformate (3.86 mL, 10 eq) were added and the reaction mixture was stirred overnight. The reaction mixture was poured onto crushed ice and then extracted with dichloromethane (50 mL). The organic layer was washed sequentially with water (2×50 mL), 4% sodium carbonate (50 mL), water (50 mL), and brine (50 mL) and then concentrated under reduced pressure. The residue was purified by automated flash chromatography (silica gel eluted with a linear gradient of 0-25% CMA in chloroform, 2500 mL) followed by recrystallization from acetonitrile to provide 0.815 g of ethyl 2-ethyl-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-4-ylcarbamate as a white crystalline solid, mp 185-187° C. Anal calcd for C20H27N5O4S: C, 55.41; H, 6.28; N, 16.15. Found: C, 55.30; H, 6.29; N, 16.24.

Workup

  1. temperaturea chilled
  2. customto give a clear solution
  3. customto come to ambient temperature
  4. stirringthe reaction mixture was stirred overnight
  5. additionThe reaction mixture was poured
  6. customonto crushed ice
  7. extractionextracted with dichloromethane (50 mL)
  8. washThe organic layer was washed sequentially with water (2×50 mL), 4% sodium carbonate (50 mL), water (50 mL), and brine (50 mL)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by automated flash chromatography (silica gel
  11. washeluted with a linear gradient of 0-25% CMA in chloroform
  12. custom2500 mL) followed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-b3a2a515971a4b6bb7b165734e058007
Source dataset
uspto-grants-2012_05
Patent number
US08188111B2

Reaction notes

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