With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.7063-99-2,Ethyl 5-phenylisoxazole-3-carboxylate,as a common compound, the synthetic route is as follows.
7063-99-2, Acetophenone (3 g, 25 mmol) was taken up in 30 mL of dry toluene and NaH (780 mg, 32 mmol) was then added. The resulting reaction mixture was stirred at room temperaturefor 60 minutes. A solution of diethyl oxalate (5.5 g, 37.5 mmol) in dry toluene (25 mL) was then added drop wise and stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with ice water. The precipitated solids were collected by filtration and dried to afford 2.85 g of ethyl 2,4-dioxo-4-phenylbutanoate (52%yield) as a yellow solid. This material (2.85 g, 12.9 mmol) was taken up in EtOH (25 mL) along with NH2OH.HC1 (1.16 g, 16.8 mmol) and then stirred under reflux for 3 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was diluted with water and extracted with EtOAc. The combined organic layers were washed with H20, dried (Na2SO4) and concentrated under reduced pressure. Purification by silica gelchromatography (pentanes/EtOAc) afforded ethyl 5-phenylisoxazole-3 -carboxylate (2.53 g,90% yield) as a white solid. This material (2.53 g, 11.6 mmol) was taken up in THF/H20 (45 mL/5 mL) along with LiOH.H20 (1.0 g, 23.3 mmol) and the resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then concentrated under reduced pressure. Sufficient 1 N HC1 was added to the resulting residue to bring the pH toabout 5. The resulting solids were collected by filtration and dried under high vacuum to afford1.5 g of 5-phenylisoxazole-3-carboxylic acid (69%) as a white solid. 5-Phenylisoxazole-3- carboxylic acid was then coupled with (4Z,7Z,1OZ,13Z,16Z,19Z)-N-(2-(((R)-3-amino-4-((1,3- dihydroxypropan-2-yl)amino)-2-methyl-4-oxobutan-2-yl)disulfanyl)ethyl)docosa- 4,7,10,13,16,19-hexaenamide using the same general amide coupling procedure describedearlier (see example 8) to obtain N-((R)-1-((1,3-dihydroxypropan-2-yl)amino)-3-((2- ((4Z,7Z, 1 OZ, 1 3Z, 1 6Z, 1 9Z)-docosa-4,7, 10,13,16,1 9-hexaenamido)ethyl)disulfanyl)-3 -methyl-ioxobutan-2-yl)-5-phenylisoxazole-3 -carboxamide. MS (El) calc? d for C49H58N40652 778.38; found 779 [M+H].
The synthetic route of 7063-99-2 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; CATABASIS PHARMACEUTICALS, INC.; VU, Chi, B.; JIROUSEK, Michael, R.; LIU, Feng; (0 pag.)WO2016/86136; (2016); A1;,
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