2,6-DIMETHYL-PYRIDIN-4-YLAMINE

4808-64-4

3512-80-9

The general procedure for the synthesis of 2,6-dimethyl-4-aminopyridine from 2,6-dimethyl-4-nitropyridine 1-oxide was as follows: 4-nitro-2,6-dimethylpyridine-N-oxide (11.0 g, 65.4 mmol) was dissolved in 50 mL of acetic acid, and powdered iron (21.8 g, 390 mmol) was added in batches, while stirring rapidly and heating gradually to 50 °C (note: the reaction becomes exothermic at this temperature). After the exotherm ceased, heating was continued at 80 °C for 1 hour. Upon completion of the reaction, 50 mL of water was added to treat the cured mixture and the suspension was filtered through diatomaceous earth. The filtrate was adjusted to pH > 12 with about 200 mL of 6N sodium hydroxide solution to form a green suspension. The suspension was extracted with chloroform (3 x 300 mL), the organic phases were combined, dried with magnesium sulfate, filtered and concentrated under reduced pressure to give pale yellow crystals (5.70 g, 71% yield). Subsequently, 2,6-dimethylpyridin-4-ylamine (2.00 g, 16.4 mmol) was dissolved in 5 mL of acetic acid, and a 2N acetic acid solution of bromine (0.84 mL, 16.3 mmol) was added dropwise, and the reaction was carried out in a room-temperature water bath for 10 min. after 1 hr, the reaction mixture was treated with 40 mL of a 20% sodium hydroxide solution, and was extracted with dichloromethane (3 × 100 mL) Extraction. The organic phases were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid (containing starting material, target product and dibromo by-product in the ratio of 1:3:1) was dissolved in 100 mL of hot hexane and the insoluble material was removed by hot filtration. The filtrate was cooled to room temperature and the title product was precipitated as fine white needle-like crystals (1.30 g, 40% yield).