Sodium methanethiolate → 6-benzyloxy-N-[5-(methylthio)pentyl]-3-nitroquinolin-4-amine

HRID 2383144Notes

Reaction equation

HRID 2383144 reaction equation
[CH3:1][S-:2].[Na+].[CH2:4]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[CH:17][C:16]([N+:22]([O-:24])=[O:23])=[C:15]2[NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]Cl)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>CN(C=O)C>[CH2:4]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[CH:17][C:16]([N+:22]([O-:24])=[O:23])=[C:15]2[NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][S:2][CH3:1])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolate2×HCID 670510456-benzyloxy-N-(5-chloropentyl)-3-nitroquinolin-4-amine

Product 1

HCID 670510536-benzyloxy-N-[5-(methylthio)pentyl]-3-nitroquinolin-4-amineYield 79.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, solid sodium thiomethoxide (1.38 g, 18.7 mmol, 95% pure) was added to a solution of 6-benzyloxy-N-(5-chloropentyl)-3-nitroquinolin-4-amine (6.24 g, 15.6 mmol) in DMF. The reaction was stirred at ambient temperature for 30 minutes and then heated at 80° C. for one hour, at which time a yellow precipitate formed. The reaction mixture was partitioned between water (390 mL) and dichloromethane (150 mL). The aqueous layer was washed with dichloromethane (100 mL), and the combined organic fractions were washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a red oil. An analysis by nuclear magnetic resonance spectroscopy indicated the presence of a large amount of starting material. The reaction product was dissolved in DMF (78 mL), treated with sodium thiomethoxide, and heated at reflux for two hours. The work-up described above was repeated, and the crude product was purified by column chromatography on silica gel (eluting with 70:30 ethyl acetate:hexane) to provide 5.1 g of 6-benzyloxy-N-[5-(methylthio)pentyl]-3-nitroquinolin-4-amine as a yellow oil.

Workup

  1. temperatureheated at 80° C. for one hour, at which time a yellow precipitate
  2. customformed
  3. customThe reaction mixture was partitioned between water (390 mL) and dichloromethane (150 mL)
  4. washThe aqueous layer was washed with dichloromethane (100 mL)
  5. washthe combined organic fractions were washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a red oil
  10. temperatureheated
  11. temperatureat reflux for two hours
  12. customthe crude product was purified by column chromatography on silica gel (eluting with 70:30 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-cd7749a95e0747a6b812f2a0ad87db50
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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