新产品编号:2052363

Chemical Name: N-[2-(2-Benzoxazolyl)tetrahydrofuran-2-ylcarbonyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:N-Boc-L-tyrosine tert-butyl ester (I) was converted to the aryl triflate (II) by means of trifluoromethanesulfonic anhydride and pyridine.Palladium-catalyzed coupling of triflate (II) with 2,6-dimethoxyphenylboronic acid (III) furnished the biphenyl compound (IV).The N-Boc protecting group of (IV) was then selectively removed by treatment with sulfuric acid in tert-butyl acetate,yielding amino ester (V).

合成路线:Coupling of 2-tetrahydrofuroic acid (VI) with ortho-aminophenol (VII) by means of PyBOP gave the corresponding ortho-hydroxyanilide (VIII),which was cyclized to the benzoxazole (IX) in the presence of DEAD and triphenylphosphine.The lithium derivative of (IX) was acylated with methyl chloroformate to produce the carboxylate ester (X).Acid (XI),generated by basic hydrolysis of ester (X),was then coupled with amino ester (V) to afford amide (XII).The tert-butyl ester group of (XII) was finally cleaved to the title carboxylic acid by treatment with trifluoroacetic acid.