IVL-745

Chemical Name: 3-[N-(3,4-Dimethoxybenzyl)-N-[2-[2-[3-methoxy-4-[3-(2-methylphenyl)ureido]phenyl]acetamido]acetyl]amino]propionic acid; N-(3,4-Dimethoxybenzyl)-N-[2-[2-[3-methoxy-4-[3-(2-methylphenyl)ureido]phenyl]acetyl]glycyl]-beta-alanine
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:Reaction of 2-nitroanisole (I) with methyl dichloroacetate (II) in the presence of potassium tert-butoxide at -5 C produced the arylacetic acid derivative (III).Hydrogenation of (III) over Pd/C produced both reduction of the nitro group and hydrogenolysis of the halogen atom to afford amine (IV),which was then condensed with o-tolyl isocyanate (V) giving urea (VI).Basic hydrolysis of the methyl ester of (VI) provided the corresponding acid (VII).This was coupled with glycine methyl ester (VIII) using EDC and HOBt to yield amide (IX).Then,ester (IX) hydrolysis with LiOH gave rise to carboxylic acid.

合成路线:Treatment of Wang resin with acryloyl chloride (XI) in the presence of diisopropyl ethylamine produced the acrylate bound resin (XII).Conjugate addition of 3,4-dimethoxybenzylamine (XIII) to the acrylate (XII) afforded the beta-amino ester resin (XIV).This was coupled with the intermediate carboxylic acid (X) employing O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) to furnish (XV).The title compound was finally liberated from the resin (XV) by cleavage with trifluoroacetic acid.