Reacción #2186209

Ecuación de reacción

POCl3

3-{4-[3-(tetrahydro-pyran-2-yloxy)-propyl]-piperazin-1-yl}-phenol

benzothiazol-2-yl-acetic acid methyl ester

piperidine

→

desired product

Rendimiento 17.0%

3-Benzothiazol-2-yl-7-[4-(3-hydroxy-propyl)-piperazin-1-yl]-chromen-2-one

Rendimiento 17.0%

Disolventes

DMF

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroevaporated
2. 2
   workup.STIRRINGthe reaction mixture stirred for 30 minutes at 90° C.
3. 3
   Otrobefore being evaporated
4. 4
   workup.STIRRINGstirred for two hours in the presence of 1 mL of a 6N aqueous HCl solution
5. 5
   Otroevaporated
6. 6
   Lavadowashed with aqueous sodium bicarbonate and saline
7. 7
   OtroThe organic phase is evaporated
8. 8
   Otrothe residue column chromatographed (silica gel, dichloromethane/EtOH/aq. NH3 90:9.9:0.1)

Procedimiento

320 mg (1 mmol) 3-{4-[3-(tetrahydro-pyran-2-yloxy)-propyl]-piperazin-1-yl}-phenol is dissolved in 10 mL DMF and treated below 10° C. with 0.1 mL POCl3. The reaction mixture is stirred at room temperature for 6 hours, then evaporated and the crude product taken up in 10 mL acetonitrile and treated with 0.6 mL (6 eq.) piperidine. 207 mg benzothiazol-2-yl-acetic acid methyl ester in 10 mL toluene are added and the reaction mixture stirred for 30 minutes at 90° C. before being evaporated. The residue is taken up in 20 mL anhydrous THF, stirred for two hours in the presence of 1 mL of a 6N aqueous HCl solution and evaporated. The residue is taken up in dichloromethane and washed with aqueous sodium bicarbonate and saline. The organic phase is evaporated and the residue column chromatographed (silica gel, dichloromethane/EtOH/aq. NH3 90:9.9:0.1) to yield 70 mg (17%) desired product as a yellow-orange powder.

Fuente