Chloroform → (11S)-11-methyl-8,9,10,11-tetrahydropyrazino[1',2':1,2]imidazo[4,5-c]quinoline

HRID 221560Notes

Reaction equation

HRID 221560 reaction equation
ClC[C:3]1[N:4]([C@@H:16]([CH3:26])[CH2:17][NH:18][C:19](=O)OC(C)(C)C)[C:5]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:15]=1.C(Cl)(Cl)Cl>Cl.CCO>[CH3:26][C@@H:16]1[N:4]2[C:5]3[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[N:8]=[CH:7][C:6]=3[N:15]=[C:3]2[CH2:19][NH:18][CH2:17]1

Participants

5

Reactant 2

HCID 6212ChloroformHCID 86624123tert-butyl (2S)-2-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propylcarbamate

Product 1

HCID 67156361(11S)-11-methyl-8,9,10,11-tetrahydropyrazino[1',2':1,2]imidazo[4,5-c]quinolineYield 65.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

tert-Butyl (2S)-2-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propylcarbamate (2.54 g, 6.77 mmol) was dissolved in 2.2 M HCl in EtOH (50 mL) and the solution was heated to reflux for 15 minutes. N2 was bubbled through the reaction for 15 minutes, and the remaining volatiles were removed under reduced pressure. The resulting material was partitioned between dichloromethane and water. The organic layer was discarded and the aqueous layer was treated with concentrated NH4OH solution to adjust to pH 11. The aqueous layer was extracted with dichloromethane (3×100 mL), and the combined organic layers were washed with brine. Triethylamine (4 mL) was then added to the solution and it was stirred at ambient temperature overnight. The reaction was washed successively with water (2×100 mL) and brine. The organic layer was dried over Na2SO4, filtered, and concentrated to give an orange foam. Chromatography (SiO2, 20-50% CMA/CHCl3) gave (11S)-11-methyl-8,9,10,11-tetrahydropyrazino[1′,2′:1,2]imidazo[4,5-c]quinoline (1.06 g) as an orange foam.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 15 minutes
  3. customN2 was bubbled through the reaction for 15 minutes
  4. customthe remaining volatiles were removed under reduced pressure
  5. customThe resulting material was partitioned between dichloromethane and water
  6. additionthe aqueous layer was treated with concentrated NH4OH solution
  7. extractionThe aqueous layer was extracted with dichloromethane (3×100 mL)
  8. washthe combined organic layers were washed with brine
  9. additionTriethylamine (4 mL) was then added to the solution and it
  10. washThe reaction was washed successively with water (2×100 mL) and brine
  11. dry with materialThe organic layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give an orange foam

Sources & evidence

ORD record
ord-d245b55739bc40128ea04b571597f60c
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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