Introduction of a new synthetic route about 6-Chloro-4-methoxypyridin-3-amine

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1256805-54-5, 6-Chloro-4-methoxypyridin-3-amine, and friends who are interested can also refer to it.

Reference of 1256805-54-5, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1256805-54-5, name is 6-Chloro-4-methoxypyridin-3-amine. A new synthetic method of this compound is introduced below.

Trimethylaluminum (7.6 mL, 2.0 M in toluene, 15 mmol) was added slowly to a 0 C. mixture of 6-chloro-4-methoxypyridin-3-amine (2.4 g, 15 mmol) and propionitrile (1.16 mL, 16.1 mmol). The flask was removed from the ice bath, allowed to warm to rt over 5 min, then was stirred at 105 C. for 17 hours. The mixture was cooled to 0 C. and THF (15 mL) was added very slowly followed by water (1 mL), 15 wt % aqueous NaOH (1 mL) and water (3 mL), stirring for 10 min after each addition. The resulting mixture was allowed to warm to rt over 30 min with stirring, then Celite was added, and the mixture stirred an additional 30 min. The mixture was then filtered through Celite with THF and concentrated. The residue was diluted with water and the pH adjusted to pH 1-2 by the addition of 1 N aqueous HCl. The solution was then washed twice with EtOAc and the aqueous layer pH adjusted to pH 10-11 by the addition of 1 N aqueous NaOH. The aqueous solution was then extracted four times with DCM, the organic layers combined, dried with anhydrous Na2SO4, filtered and concentrated to provide the title compound, which was used without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1256805-54-5, 6-Chloro-4-methoxypyridin-3-amine, and friends who are interested can also refer to it.

Reference:
Patent; Janssen Pharmaceutica NV; Goldberg, Steven; Martin, Connor L.; Fennema, Elizabeth G.; Kummer, David A.; Nishimura, Rachel T.; Tanis, Virginia M.; Woods, Craig R.; Fourie, Anne M.; Xue, Xiaohua; (120 pag.)US2019/382354; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem