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

HRID 75436Notes

Reaction equation

[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

Participants

Conditions

Temperature: 0 °C

Procedure

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.

Workup

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)

Sources & evidence

ORD record: ord-549fb1ccdd8b49e78bf8d46a7fa0c92f
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835429B2

Reaction notes

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