Methanol → 5-Cyano-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester

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Reaction Steps

A degassed suspension of 5-chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester (1.35 g, 3.82 mmol), zinc (II) cyanide (492.8 mg, 4.2 mmol, 1.1 eq.), and Pd(PPh3)4 (551.0 mg, 0.48 mmol, 0.12 eq.) in anhydrous dimethylformamide (30 mL) was subjected to microwave irradiation at 150° C. for 18 minutes. The reaction mixture was poured into ethyl acetate and then filtered through a pad of Celite®. The pad was rinsed well with ethyl acetate (2×). The combined filtrates were washed with 50% brine (2×) and brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% ethyl acetate in hexane) to give a brown oil. Trituration with MeOH afforded the desired compound as an orange solid (1.31 g, 99.8%). 1H NMR (CDCl3, 400 MHz) δ ppm 10.56 (s, 1H), 8.36 (s, 1H), 8.29 (t, J=7.82 Hz, 1H), 7.37-7.27 (m, 2H), 4.10 (s, 3H), 0.29 (s, 9H); LCMS (method D1): RT=1.28 min, [M+H]+=345.

Provenance & Evidence