Reacción #628077

Ecuación de reacción

4-benzyloxyaniline

Diisopropyl azodicarboxylate

2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol

triphenylphosphine

3-(methylthio)propan-1-ol

2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol

3-benzyloxyaniline

ethoxyacetyl chloride

3-methoxypropanoyl chloride

→

2-(2-methoxyethyl)-7-[3-(methylthio)propoxy]-1-propyl-1H-imidazo[4,5-c]quinoline

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITat room temperature for 16 hours
2. 2
   OtroThe solvent was removed under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
4. 4
   workup.ADDITIONtreated with 1 M hydrochloric acid (40 mL)
5. 5
   workup.STIRRINGstirred for 30 minutes
6. 6
   OtroThe layers were separated
7. 7
   Extracciónthe aqueous layer was extracted with ethyl acetate (2×25 mL)
8. 8
   Extracciónwas extracted with dichloromethane (3×50 mL)
9. 9
   Lavadowashed with water and saturated aqueous sodium chloride
10. 10
    Secadodried over anhydrous sodium sulfate
11. 11
    Filtraciónfiltered
12. 12
    Concentraciónconcentrated under reduced pressure
13. 13
    OtroThe crude product was purified by flash chromatography (silica gel, gradient elution with 1-4% methanol in dichloromethane)

Procedimiento

A modification on the methods described in Parts A-H of Example 2 were used to prepare 2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol, with 3-benzyloxyaniline and 3-methoxypropanoyl chloride used in lieu of 4-benzyloxyaniline and ethoxyacetyl chloride, respectively. Diisopropyl azodicarboxylate (2.07 mL, 10.5 mmol) was added dropwise to a slurry of 2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol (2.00 g, 7.01 mmol), triphenylphosphine (2.75 g, 10.5 mmol), and 3-(methylthio)propan-1-ol (1.08 mL, 10.5 mmol) in tetrahydrofuran (70 mL) at 0° C. The solution was stirred for 30 minutes at 0° C., then at room temperature for 16 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, treated with 1 M hydrochloric acid (40 mL), and stirred for 30 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The aqueous layer was adjusted to approximately pH 14 with 50% aqueous sodium hydroxide and then was extracted with dichloromethane (3×50 mL). The organic layers were combined, washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution with 1-4% methanol in dichloromethane) to provide 2.0 g of 2-(2-methoxyethyl)-7-[3-(methylthio)propoxy]-1-propyl-1H-imidazo[4,5-c]quinoline as an opaque solid.

Fuente