Reacción #996521

Ecuación de reacción

7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine

1,4-butanesultam

(±)-trans-1,2-diaminocyclohexane

potassium phosphate

→

7-(1,1-dioxo-[1,2]thiazinan-2-yl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine

Rendimiento 55.5%

Disolventes

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe vial was flushed with nitrogen
2. 2
   Otrosealed with a Teflon-
3. 3
   Otrolined cap
4. 4
   Otroplaced in an oil bath
5. 5
   TemperaturaThe reaction was cooled to ambient temperature
6. 6
   workup.ADDITIONdiluted with chloroform
7. 7
   Filtraciónfiltered through a bed of CELITE
8. 8
   Filtraciónfilter agent
9. 9
   OtroThe solvent was evaporated
10. 10
    Otrothe residue was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument
11. 11
    OtroThe purification
12. 12
    Lavadowas carried out eluting with chloroform
13. 13
    OtroAdditional purification
14. 14
    Otroby recrystallization from acetonitrile

Procedimiento

7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.75 g), 1,4-butanesultam (0.29 g), copper(I) iodide (68 mg), (±)-trans-1,2-diaminocyclohexane (42 μL), potassium phosphate (0.79 g) and dioxane (4 mL) were added to a scintillation vial. The vial was flushed with nitrogen, sealed with a Teflon-lined cap, placed in an oil bath, and heated at 110° C. for 30 hours. The reaction was cooled to ambient temperature, diluted with chloroform and filtered through a bed of CELITE filter agent. The solvent was evaporated and the residue was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument using a silica gel cartridge. The polar component of the eluent was chloroform:methanol:ammonium hydroxide 80:18:2 (CMA). The purification was carried out eluting with chloroform:CMA in a gradient from 99:1 to 90:10. Additional purification by recrystallization from acetonitrile provided 0.47 g of 7-(1,1-dioxo-[1,2]thiazinan-2-yl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine as pale yellow crystals, mp 172-174° C.

Fuente