6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine synthesis

Yield:212779-33-4 48.6%

Reaction Conditions:

with dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂;potassium carbonate in water;acetonitrile at 100; for 6 h;Suzuki Coupling;

Steps:

General procedure for the synthesis of intermediate 7

A suspension of 3-bromo-6-chloropyrazin-2-amine 1 (5g, 24mmol), (2,3-dichlophenyl)boronic acid 6 (5.5g, 28.8mmol), potassium carbonate (9.95g, 72mmol), and PdCl₂(dppf) DCM adduct (1.175g, 1.44mmol) in MeCN:H₂0 (5:1, 90mL, degassed) was stirred for 6h at 100°C and then cooled to room temperature, the reaction was filtered and filtrates were concentrated under reduced pressure, the resulting residue was purified by flash column chromatography (petroleum ether: ethyl acetate=5:1) to give 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine 7 as a yellow compound (3.2g, 11.66mmol, 48.6% yield). ¹H NMR (400MHz, CDCl₃) δ 7.41 (dd, J=8.0, 1.7Hz, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.22 (dd, J=8.2, 1.7Hz, 1H), 5.21 (s, 2H).

References:

Tang, Kai;Zhao, Min;Wu, Ya-Hong;Wu, Qiong;Wang, Shu;Dong, Yu;Yu, Bin;Song, Yihui;Liu, Hong-Min [European Journal of Medicinal Chemistry,2022,vol. 230,art. no. 114106]