反应详情

温度

110 °C

The freshly formed N,N-BisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine XV (2.67 mmol based on 100% conversion, 2.0 equiv based on bromide) was dissolved in 20 Ml of 1,2-dimethoxyethane and to that solution was added tert-butyl (6-bromoimidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate IV (707 mg, 1.34 mmol, 1.0 equiv), Na2CO3 (283 mg, 2.67 mmol, 2.0 equiv), Pd(PPh3)4 (155 mg, 0.134 mmol, 0.1 equiv) and water (10 mL) and the solution was degassed for 5 min using N2 gas. The reaction was then placed under N2 atmosphere and heated at 110° C. for 90 min. LCMS showed complete consumption of the bromide starting material and the reaction was removed from heat and allowed to cool to RT. The reaction was diluted with 100 mL water and 100 mL 20% MeOH/DCM and the organic layer was recovered, extracted 1× sat. NaHCO3, 1× sat brine and then dried over Na2SO4. The solution was then filtered and concentrated down to an orange-red solid. The sample was then slurried in warm MeOH, sonicated then filtered, washing 2×20 mL with cold MeOH and then the cream-colored solid was dried on hi-vacuum overnight to yield 905 mg of tert-butyl (6-(6-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate XVI.

1. customthe solution was degassed for 5 min
2. customconsumption of the bromide starting material
3. customthe reaction was removed
4. temperaturefrom heat
5. temperatureto cool to RT
6. additionThe reaction was diluted with 100 mL water and 100 mL 20% MeOH/DCM
7. customthe organic layer was recovered
8. extractionextracted 1× sat. NaHCO3, 1×
9. dry with materialdried over Na2SO4
10. filtrationThe solution was then filtered
11. concentrationconcentrated down to an orange-red solid
12. customsonicated
13. filtrationthen filtered
14. washwashing 2×20 mL with cold MeOH
15. customthe cream-colored solid was dried on hi-vacuum overnight