反应详情

温度

90 °C

A small microwave vial was charged with Pd2(dba)3 (0.064 g, 0.070 mmol), xantphos (0.081 g, 0.140 mmol). The vial was sealed with a septum cap and 0.3 mL dioxane was added. The vial was heated at 90° C. in an oil bath for 3 min. The solution was then cooled to rt. A separate vial was charged with 5-bromo-2-((4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)amino)benzaldehyde (1.26 g, 2.81 mmol) and sealed with a septum cap. The vial was flushed with N2 and 1,4-dioxane (9.36 ml), phenylmethanethiol (0.399 ml, 3.37 mmol) and dipea (1.471 ml, 8.42 mmol) were added. The pre-activated catalyst solution prepared in the microwave vial was transferred to the vial containing the reactants via syringe and the resulting mixture was heated at 90° C. for 3 h. The reaction mixture was partitioned between 1 N HCl/brine (20 mL) and EtOAc (30 mL). The layers were separated and the aqueous layer was extracted with EtOAc (1×20 mL). The combined organic layers were dried (Na2SO4) and concentrated for purification by MPLC (Biotage Isolera). The crude residue was taken up in minimal DCM and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® Gold pre-packed silica gel column (80 g) using 100% Heptane to 60:40 Heptane: EtOAc gradient to afford 5-(benzylthio)-2-((4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)amino)benzaldehyde as a bright yellow foam. (ESI) 490.2 (M−H)−.

1. customThe vial was sealed with a septum
2. customcap
3. temperatureThe solution was then cooled to rt
4. customsealed with a septum
5. customcap
6. additionwere added
7. customThe pre-activated catalyst solution prepared in the microwave vial
8. additioncontaining the reactants via syringe
9. temperaturethe resulting mixture was heated at 90° C. for 3 h
10. customThe reaction mixture was partitioned between 1 N HCl/brine (20 mL) and EtOAc (30 mL)
11. customThe layers were separated
12. extractionthe aqueous layer was extracted with EtOAc (1×20 mL)
13. dry with materialThe combined organic layers were dried (Na2SO4)
14. concentrationconcentrated for purification by MPLC (Biotage Isolera)
15. customabsorbed onto a 25 g loading cartridge