Reacción #1605833

Ecuación de reacción

aripiprazole

triethylamine

ethyl isocyanate

→

7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-N-ethyl-3,4-dihydro-2-oxoquinoline-1(2H)-carboxamide

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was quenched with water
2. 2
   Extracciónextracted with dichloromethane (3×20 mL)
3. 3
   Lavadowashed with saturated aqueous sodium hydrogen carbonate (20 mL) and brine (20 mL)
4. 4
   Secadodried over MgSO4
5. 5
   Concentraciónconcentrated
6. 6
   OtroThe product was purified by column chromatography on silica eluting with 0-3% methanol in 1:1 ethyl acetate to dichloromethane
7. 7
   OtroThe product was triturated in heptane
8. 8
   Otroto remove aliphatic impurities
9. 9
   Filtraciónfiltered
10. 10
    Otrodried
11. 11
    workup.DISSOLUTIONThe material was dissolved in ethyl acetate
12. 12
    Lavadowashed with saturated aqueous sodium hydrogen carbonate (6×15 mL)
13. 13
    Otroto afford Compound-72 (0.482 g) as a pink solid

Procedimiento

To a solution of aripiprazole (1.5 g, 3.35 mmol) in dichloromethane (33 mL) was added triethylamine (0.56 mL, 4.01 mmol) and ethyl isocyanate (0.53 mL, 6.69 mmol). The reaction was stirred at room temperature for 5 days. The reaction was quenched with water and extracted with dichloromethane (3×20 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate (20 mL) and brine (20 mL), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 0-3% methanol in 1:1 ethyl acetate to dichloromethane. The product was triturated in heptane to remove aliphatic impurities and then filtered and dried. The material was dissolved in ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate (6×15 mL) to afford Compound-72 (0.482 g) as a pink solid.

Fuente