반응 #79894

반응 방정식

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

수율 61.0%

용매

dichloroethane

water

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 15 minutes at 0° C.
2. 2
   기타after which the ice bath was removed
3. 3
   온도to 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
   기타The organic layer was evaporated under reduced pressure
8. 8
   workup.ADDITIONEthyl acetate was added
9. 9
   기타the layers were partitioned
10. 10
    추출the aqueous layer was extracted with ethyl acetate
11. 11
    세척washed with water and brine
12. 12
    건조dried over magnesium sulfate
13. 13
    여과filtered
14. 14
    기타evaporated under reduced pressure
15. 15
    기타The compound was purified by flash chromatography on silica

실험 절차

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

출처