反应详情

温度

80 °C

A vial containing 8-bromo-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.030 g, 0.076 mmol, prepared using D from Preparation #BBBBB.1 and NaOH, GGG.1 with NBS, K.1 with TsCl and NaH), 2-(4-methylpiperazin-1-yl)-4-(tributylstannyl)pyrimidine (0.054 g, 0.12 mmol, Preparation #39), LiCl (0.010 g, 0.24 mmol), CuI (0.003 g, 0.02 mmol), CsF (0.017 g, 0.12 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) under nitrogen was evacuated and then back-filled with nitrogen. 1,4-Dioxane (0.5 mL) was added and nitrogen was bubbled through the mixture for about 30 min. The reaction vessel was sealed and the mixture was warmed to about 80° C. After about 4 h, the mixture was allowed to cool to ambient temperature. The mixture was diluted with water (5 mL) and EtOAc (5 mL) and then filtered through a syringe filter. The layers were separated and the aqueous phase was extracted with EtOAc (5 mL). The combined organics were concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM over 40 min to afford 8-(2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.026 g, 69%): LC/MS (Table 1, Method n) Rt=0.56 min; MS m/z 490 (M+H)+.

1. customwas evacuated
2. additionback-filled with nitrogen
3. addition1,4-Dioxane (0.5 mL) was added
4. customnitrogen was bubbled through the mixture for about 30 min
5. customThe reaction vessel was sealed
6. temperatureto cool to ambient temperature
7. additionThe mixture was diluted with water (5 mL) and EtOAc (5 mL)
8. filtrationfiltered through a syringe
9. filtrationfilter
10. customThe layers were separated
11. extractionthe aqueous phase was extracted with EtOAc (5 mL)
12. concentrationThe combined organics were concentrated under reduced pressure
13. customThe residue was purified by silica gel chromatography
14. washeluting with a gradient of 0-10% MeOH in DCM over 40 min