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

Reaktionsgleichung

[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])[N:3]=1.Cl.[CH:15]12[O:22][CH:19]([CH2:20][CH2:21]1)[CH2:18][NH:17][CH2:16]2.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[N:7]=[C:6]([N:17]2[CH2:16][CH:15]3[O:22][CH:19]([CH2:20][CH2:21]3)[CH2:18]2)[CH:5]=[C:4]([CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])[N:3]=1

Komponenten

Reaktionsbedingungen

Temperatur: 0 °C

Versuchsvorschrift

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.

Aufarbeitung

temperatureto warm to room temperature over 30 minutes
temperaturethen heated
temperatureto reflux for 1.5 hours
concentrationconcentrated
custompurified by chromatography on silica gel (eluting with 2-3% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag: ord-549fb1ccdd8b49e78bf8d46a7fa0c92f
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08835429B2

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