Related Products of 38749-90-5, 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. 38749-90-5, name is 5-Bromo-2-ethylpyridine. A new synthetic method of this compound is introduced below.
In a 2 L flask was added 2,5-dibromopyridine (60 g, 235 mmol) and 800 mL of triethylamine. The solution was degassed via purging with a stream of nitrogen through the solution for 30 minutes. The reaction was charged with trimethylsilylacetylene (36 mL, 255 mmol) followed by PdCl2(PPh3)2 (3 g, 4.27 mmol) and cuprous iodide (1 g, 5.26 mmol). The reaction was stirred for 10 minutes and an exotherm began. The temperature of the reaction was not allowed to exceed 30 C. by cooling in a water bath. The thick reaction mixture was stirred for 2 hours and LC showed completion. The reaction was poured into water and extracted with ethyl acetate (2×400 mL) The combined organic layers were washed with water (3×500 mL), dried over sodium sulfate, filtered and solvent removed under reduced pressure. The residue was purified by passing through a plug of silica gel (200 g) eluting with heptane followed by 5% ethyl acetate heptane to give 5-bromo-2-((trimethylsilyl)ethynyl)pyridine. Yield 58 g, 97%In a flask was added 5-bromo-2-((trimethylsilyl)ethynyl)pyridine (30 g, 118 mmol), 200 mL of ethanol, and solid sodium hydroxide (5 g, 125 mmol). The reaction was stirred for 2 hours, and then poured into water and the pH was adjusted to 6 by the addition of 1 N hydrochloric acid. The mixture was washed with diethyl ether (2×300 mL) and the combined organic layers were dried over sodium sulfate and solvent removed under reduced pressure. The product, 5-bromo-2-ethylnylpyridine, was used without further purification. Yield 20 g, 93%5-Bromo-2-ethylnylpyridine (10 g, 54.9 mmol) was dissolved in ethanol (100 mL) and Adam’s Catalyst (PtO2, 75%, 1 g) was added. The mixture was hydrogenated at 3 psi of hydrogen, continually checking the progress of the reaction by LC and 1H NMR between each charge of hydrogen. After 10 psi was consumed, the data showed completion of the reaction with <5% of reduction of the bromine. The catalyst was filtered off and the solvent was removed under reduced pressure at 20 C. to give 5-bromo-2-ethylpyridine. Yield 8.7 g, 85%.In a 1 L round-bottomed flask was 5-bromo-2-ethylpyridine (10 g, 53.8 mmol) and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (13.83 g, 59.1 mmol) in Dioxane (300 ml) followed by saturated sodium bicarbonate (150 ml). The mixture was degassed by passing a stream of nitrogen through the mixture for 20 minutes. Tetrakis(triphenylphosphine) palladium(0) (3.36 g, 2.91 mmol) was added and the mixture was heated to reflux becoming very thick then finally going to solution. The reaction was heated for 2 hours, cooled to room temperature and the solvent removed under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate and solvent removed under reduced pressure. The residue was purified by column chromatography 0-100% ethyl acetate/heptane to give 5-(6-ethylpyridin-3-yl)-2-methylaniline. Yield 6.7 g, 58.8%The urea was formed from 5-(6-Ethylpyridin-3-yl)-2-methylaniline and 4-(2-amino-5-tert-butylthiophene-3-carbonyl)-3,3-dimethylpiperazine-2-one.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,38749-90-5, 5-Bromo-2-ethylpyridine, and friends who are interested can also refer to it.
Reference:
Patent; LOCUS PHARMACEUTICALS, INC.; US2010/41642; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem