반응 #70244

반응 방정식

4-Methylsulfonyl-piperidine hydrochloride

sodium tert-butoxide

4-bromo-1-(2-(methylthio)pyrimidin-4-yl)-1H-indole

→

desired compound

수율 43.6%

4-(4-methanesulfonyl-piperidin-1-yl)-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indole

수율 43.6%

용매

dioxane

dioxane

dioxane

반응 조건

후처리

1. 1
   기타the mixture was bubbled with argon for 10 minutes
2. 2
   기타The mixture was bubbled with argon for 5 minutes
3. 3
   기타sealed
4. 4
   기타The sealed thick wall bottle was put into oil bath at 65° C.
5. 5
   workup.STIRRINGThe mixture was stirred at 120° C. for 1.5 hr
6. 6
   온도The resulting mixture was cooled to 50° C.
7. 7
   여과filtered through a thin layer of Celite
8. 8
   세척rinsed with dioxane (100 mL)
9. 9
   농축The filtrate was concentrated
10. 10
    추출extracted with dichloromethane and saturated ammonium chloride solution
11. 11
    기타The organic layer was dried
12. 12
    농축concentrated to a volume about 25 mL
13. 13
    workup.ADDITIONThe mixture was treated with ethyl acetate (150 mL)
14. 14
    여과the yellow solid was filtered

실험 절차

4-Methylsulfonyl-piperidine hydrochloride (6.89 g, 34.5 mmol) was grinded into fine powder and mixed with fine powder of sodium tert-butoxide (7.65 g, 79.6 mmol) in dry dioxane (180 mL). After 30 minutes of stirring, 4-bromo-1-(2-(methylthio)pyrimidin-4-yl)-1H-indole (8.5 g, 26.5 mmol) was added followed by dry dioxane (10 mL) and the mixture was bubbled with argon for 10 minutes. Bis(tri-tert-butylphosphine)palladium (1.02 g, 2.0 mmol) was added followed by dry dioxane (10 mL). The mixture was bubbled with argon for 5 minutes and then sealed. The sealed thick wall bottle was put into oil bath at 65° C. and heated to 120° C. The mixture was stirred at 120° C. for 1.5 hr. The resulting mixture was cooled to 50° C. and filtered through a thin layer of Celite, rinsed with dioxane (100 mL). The filtrate was concentrated and extracted with dichloromethane and saturated ammonium chloride solution. The organic layer was dried and concentrated to a volume about 25 mL. The mixture was treated with ethyl acetate (150 mL) and the yellow solid was filtered to give the desired compound (4.65 g). The filtrate was concentrated and dissolved in dichloromethane and purified through ISCO flash column chromatography (200 g silica gel, 20% to 100% ethyl acetate in hexanes) to give second batch of desired product as a yellow solid (1.67 g, combined total 6.32 g, yield 59.1%). LC-MS calcd for C19H22N4O2S2 (m/e) 402.12, obsd 402.9 (M+H).

출처