Reaktion #79894

Reaktionsgleichung

4-chloro-5-iodo-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidine

1-methyl-4-piperidone

acetic acid

sodium bicarbonate

1-methyl-4-piperidone

acetic acid

sodium triacetoxy borohydride

→

4-chloro-5-iodo-7-[1-(1-methyl-4-piperidinyl)-4-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidine

Ausbeute 61.0%

Lösungsmittel

dichloroethane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 15 minutes at 0° C.
2. 2
   Sonstigeafter which the ice bath was removed
3. 3
   Temperaturto warm to room temperature
4. 4
   workup.STIRRINGstirred over night
5. 5
   workup.STIRRINGstirred at room temperature
6. 6
   workup.STIRRINGstirred for 1 hour
7. 7
   SonstigeThe organic layer was evaporated under reduced pressure
8. 8
   workup.ADDITIONEthyl acetate was added
9. 9
   Sonstigethe layers were partitioned
10. 10
    Extraktionthe aqueous layer was extracted with ethyl acetate
11. 11
    Waschenwashed with water and brine
12. 12
    Trocknendried over magnesium sulfate
13. 13
    Filtrationfiltered
14. 14
    Sonstigeevaporated under reduced pressure
15. 15
    SonstigeThe compound was purified by flash chromatography on silica

Vorschrift

A mixture of 4-chloro-5-iodo-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidine (0.52 g, 1.43 mmol), 1-methyl-4-piperidone (0.178 g, 1.57 mmol), and glacial acetic acid (0.094 g, 1.57 mmol) in dichloroethane was stirred at 0° C. for 20 minutes. Sodium 15 triacetoxy borohydride (0.455 g, 2.15 mmol) was added and stirred for 15 minutes at 0° C., after which the ice bath was removed, allowed to warm to room temperature and stirred over night. Additional 1-methyl-4-piperidone (0.178 g, 1.57 mmol), glacial acetic acid (0.094 g, 1.57 mmol), and sodium triacetoxy borohydride (0.455 g, 2.15 mmol) were added and stirred at room temperature. To the reaction solution was added sodium bicarbonate (0.721 g, 8.58 mmol) in water (10 mL) and stirred for 1 hour. The organic layer was evaporated under reduced pressure. Ethyl acetate was added, the layers were partitioned, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The compound was purified by flash chromatography on silica using dichloromethane/ethyl acetate (1:1), 10% methanol in dichloromethane, and then 20% methanol in dichloromethane to give 400 mg (61%) of 4-chloro-5-iodo-7-[1-(1-methyl-4-piperidinyl)-4-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidine

Quelle