6-Amino-5-methoxy-nicotinonitrile synthesis

Yield:1256821-98-3 54%

Reaction Conditions:

with tetrakis(triphenylphosphine) palladium⁽⁰⁾ in N,N-dimethyl-formamide at 100; for 4 h;Inert atmosphere;

Steps:

I Example I: Preparation of 6-amino-5-methoxy-pyridine-3-carbonitrile

To a solution of 5-bromo-3-methoxy-pyridin-2-amine (3.00 g, 14.8 mmol) in N,N- dimethylformamide (55 mL) under a nitrogen atmosphere was added zinc (II) cyanide (2.78 g, 23.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (2.06 g, 1.77 mmol). The reaction mixture was stirred at 100°C for 4 h. The reaction mixture was diluted with ethyl acetate and washed successively with a saturated solution of ammonium hydroxide and brine. The phases were separated. The organic phases was dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / cyclohexane 1 :5) to give 6-amino-5-methoxy-pyridine-3-carbonitrile (1.2 g, 54% yield).1H NMR (400 MHz, CDC1₃): 7.99 (s, 1H), 6.99 (s, 1H), 3.88 (s, 3H) ppm. ¹³C NMR (100 MHz, CDC1₃): 152.83, 144.58, 141.27, 118.32, 115.52, 97.66, 55.65. LC-MS (Method B): RT 0.69, 150 (M+H⁺)

References:

WO2013/37755,2013,A1 Location in patent:Page/Page column 24