反应详情

A solution of benzyl [2-[2-(1-aminocyclopropyl)phenoxy]ethyl]methylcarbamate (Preparation 4b, 68.1% w/w, 102.2 mg, 204 μmol), methyl 3-(3,5-dibromo-2-oxo-1(2H)-pyrazinyl)-5-fluoro-4-methylbenzoate (Preparation 1g, 94.5 mg, 225 μmol) and N,N-diisopropylethylamine (137 μL, 818 μmol) in 1,4-dioxane (3 mL) was heated to 90° C. (jacket temperature) in a sealed reaction tube for 3 h, before being left to stir overnight at ambient temperature. Further methyl 3-(3,5-dibromo-2-oxo-1(2H)-pyrazinyl)-5-fluoro-4-methylbenzoate (8.6 mg, 20.4 μmol) was added and the reaction mixture re-heated to 90° C. (jacket temperature) for a further 90 min. The solution was then concentrated in vacuo before being purified by preparative TLC on silica, eluting with ethyl acetate/isohexane (1:2 v/v), to afford methyl 3-[3-[1-[2-[2-[(benzyloxycarbonyl)methylamino]ethoxy]phenyl]cyclopropylamino]-5-bromo-2-oxo-1(2H)-pyrazinyl]-5-fluoro-4-methylbenzoate (125.7 mg) as a white foam.

1. customin a sealed reaction tube for 3 h
2. waitbefore being left
3. temperaturethe reaction mixture re-heated to 90° C. (jacket temperature) for a further 90 min
4. concentrationThe solution was then concentrated in vacuo
5. custombefore being purified by preparative TLC on silica
6. washeluting with ethyl acetate/isohexane (1:2 v/v)