반응 #162618

반응 방정식

2,4-dichloro-6-(methylsulfonylmethyl)pyrimidine

8-oxa-3-azabicyclo[3.2.1]octane

8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride

triethylamine

→

3-(2-chloro-6-(methylsulfonylmethyl)pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

3-(2-Chloro-6-(methylsulfonylmethyl)pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   온도to warm to room temperature over 30 minutes
2. 2
   온도then heated
3. 3
   온도to reflux for 1.5 hours
4. 4
   농축concentrated
5. 5
   기타purified by chromatography on silica gel (eluting with 2-3% methanol in dichloromethane)

실험 절차

A 2,4-dichloro-6-(methylsulfonylmethyl)pyrimidine (42, prepared as reported in WO2008/023159, 1.60 g, 6.64 mmoles) was dissolved in dichloromethane and cooled to 0° C. A solution of 8-oxa-3-azabicyclo[3.2.1]octane (2, 0.990 g, 6.64 mmoles) in dichloromethane and triethylamine (1.94 mL, 13.94 mmoles) was slowly added over 15 minutes. The solution was allowed to warm to room temperature over 30 minutes then heated to reflux for 1.5 hours. The reaction mixture was stirred at room temperature for an additional 18 hours, then concentrated and purified by chromatography on silica gel (eluting with 2-3% methanol in dichloromethane) to provide 3-(2-chloro-6-(methylsulfonylmethyl)pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (43) as a white solid. Yield: 1.72 g (82%). HRMS; [M+H]+ Obs'd=318.0669, [M+H]+ Calc'd=318.0674.

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