Réaction #79894

Équation de réaction

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

Rendement 61.0%

Solvants

dichloroethane

water

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirred for 15 minutes at 0° C.
2. 2
   Autreafter which the ice bath was removed
3. 3
   Températureto 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
   AutreThe organic layer was evaporated under reduced pressure
8. 8
   workup.ADDITIONEthyl acetate was added
9. 9
   Autrethe layers were partitioned
10. 10
    Extractionthe aqueous layer was extracted with ethyl acetate
11. 11
    Lavagewashed with water and brine
12. 12
    Séchagedried over magnesium sulfate
13. 13
    Filtrationfiltered
14. 14
    Autreevaporated under reduced pressure
15. 15
    AutreThe compound was purified by flash chromatography on silica

Mode opératoire

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

Source