反应详情

温度

150 °C

A mixture of 1,1-dimethylethyl (2S)-4-({4-[[(6-bromo-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D108) (0.050 g, 0.0993 mmol), 4,4-difluoropiperidine (0.141 g, 0.894 mmol) and triethylamine (0.138 mL, 0.993 mmol) in acetonitrile (4 mL) was heated in a microwave at 150° C. for 12 h. Further portions of 4,4-difluoropiperidine (4 eq.) and triethylamine (5 eq.) were added and the reaction heated at 150° C. for 1 h. The reaction mixture was concentrated and the residue dissolved in DCM/water. The aqueous layer was further extracted with DCM (×3) and the combined organics were dried (Na2SO4) and concentrated to give a yellow gum which was purified by column chromatography. Elution with 0-100% EtOAc/hexane gave a colourless gum which was a mixture (˜9:1) of the title compound and unreacted D109 (0.0485 g). MS (ES): MH+ 544.2.

1. temperaturethe reaction heated at 150° C. for 1 h
2. concentrationThe reaction mixture was concentrated
3. dissolutionthe residue dissolved in DCM/water
4. extractionThe aqueous layer was further extracted with DCM (×3)
5. dry with materialthe combined organics were dried (Na2SO4)
6. concentrationconcentrated
7. customto give a yellow gum which
8. customwas purified by column chromatography
9. washElution with 0-100% EtOAc/hexane
10. customgave a colourless gum which