2-Methoxy-6-(methylamino)pyridine synthesis

Yield: 31%

Reaction Conditions:

in water at 170; for 7 h;Sealed tube;

Steps:

3.1 Step 1: 6-methoxy-N-methylpyridin-2-amine
A mixture of 2-chloro-6-methoxypyridine (12.0 g, 85.6 mmol) and aqueous methanamine (40%, 24 mL) was stuffed at 170 °C in sealed tube for 7 h. After cooled, themixture was diluted with water (50 mL) and then extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh, 0 to 5% methanol in dichloromethane) to afford 6-methoxy-N-methyl-pyridin-2-amine (2.7 g, 31%) as a lightyellow oil. ‘H NMR (400 MHz, CDC13) 5 7.37 (t, J = 8.0 Hz, 1H), 6.04 (d, J = 8.0 Hz, 1H),5.94 (d, J = 7.8 Hz, 1H), 4.39 (br. s, 1H), 3.86 (s, 3H), 2.90 (s, 3H).

References:

F. HOFFMANN-LA ROCHE AG;GENENTECH, INC.;PATEL, Snahel WO2018/73193, 2018, A1 Location in patent:Page/Page column 49