2-Amino-5-methylpyridine

light yellow crystalline flakes

2-Amino-5-methylpyridine is used as an intermediate in the pharmaceutical industry for the manufacture of Avosentan (used in diabetic nephropathy), Pirfenidone (anti-inflammatory, anti-oxidant and antifibrotic agent) and Zolpidem (sedative/ hypnotics). It is also used for the manufacture of Fluazuron, which is a pesticide, and for commercial purposes.

2-Amino-5-methylpyridine is obtained when 3-methyl-pyridine is reacted with sodium amide in an inert diluent at elevated temperature and elevated pressure (compare U.S. Pat. No. 4,386,209).

Poison by ingestion,subcutaneous, and skin contact routes. When heated todecomposition it emits toxic vapors of NOx.

2.2 g (0.377 mol) of trimethylamine are condensed at -10 °C. and added at -5 °C. to a solution of 10.03 g (0.092 mol) of 3-methyl-pyridine 1-oxide in 120 ml of methylene chloride. At this temperature, 7.9 (0.11 mol) of thionyl chloride in 15 ml of methylene chloride is added dropwise in 30 minutes. The temperature during this process is kept below 0 °C. The resulting yellow solution is allowed to thaw and is stirred overnight at room temperature. The solvent is removed in vacuo 35 ml of a 48% strength hydrogen bromide solution and then added. The water is distilled off, and the mixture is then heated to 210 °C. A 48% strength hydrogen bromide solution is continuously added dropwise, and water is distilled. After 8 hours, the reaction is completed according to thin-layer chromatography. The mixture is allowed to cool and is adjusted to pH 9 using a dilute sodium hydroxide solution. The mixture is then extracted four times using ethyl acetate. After filtration, the combined extracts are dried over sodium sulphate and concentrated on the rotary evaporator. 8 g (80.5% of theory) of 2-amino-5-methylpyridine are obtained.

Crystallise it from acetone. [Beilstein 22/9 V 289.]

[1] Catalysis Communications, 2013, vol. 32, p. 28 - 31
[2] Advanced Synthesis and Catalysis, 2009, vol. 351, # 11-12, p. 1722 - 1726