反应详情

温度

110 °C

Put 5 g (22.5 mmol) of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 3.2 g (23.65 mmol) of 2-methylphenyl boronic acid in 45 mL of anhydrous toluene in a screw-top bottle. After dissolution, add 34 mL (67.6 mmol) of a 2N aqueous solution of sodium carbonate and degas the two-phase mixture for 30 min by bubbling with argon. Then add 1.3 g (1.13 mmol) of Pd(PPh3)4 and stir the reaction mixture vigorously at 110° C. for 48 h. After cooling, distribute the solution in 500 mL of EtOAc/brine 1:1 mixture and extract the aqueous phase again with 4×50 mL of EtOAc. Combine the organic phases, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 0 to 20% of EtOAc. After concentration under reduced pressure, we obtain 2 g of methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylate in the form of yellow wax.

1. dissolutionAfter dissolution
2. customdegas the two-phase mixture for 30 min
3. customby bubbling with argon
4. temperatureAfter cooling
5. extractionextract the aqueous phase again with 4×50 mL of EtOAc
6. dry with materialdry over Na2SO4
7. concentrationconcentrate under reduced pressure
8. customPurify the residue
9. customobtained by silica gel column chromatography
10. washeluting with a cyclohexane/EtOAc gradient from 0 to 20% of EtOAc
11. concentrationAfter concentration under reduced pressure, we