تفاعل #2186209

معادلة التفاعل

POCl3

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

benzothiazol-2-yl-acetic acid methyl ester

piperidine

→

desired product

المردود 17.0%

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

المردود 17.0%

المذيبات

DMF

toluene

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر