MEN-11467

Chemical Name: N-[2-(4-Methylphenyl)acetyl]-N-methyl-(3-naphthyl)-L-alanine N-[2-(1H-indol-3-ylcarboxamido)cyclohexyl]amide
项目整合开发状态: Preclinical
项目研究机构: Menarini (Originator)
合成路线:3-Indolylcarboxylic acid (I) was converted to acid chloride (II) with oxalyl chloride in refluxing CH2Cl2,and subsequently condensed with cis 1,2-cyclohexanediamine (III) to provide racemic amide (IV).Coupling of (4-methylphenyl)acetyl chloride (VI) with D-3-(2-naphthyl)alanine (V) was carried out via previous silylation of the amino acid with bis(trimethylsilyl)acetamide in THF.The resulting amide (VII) was N-alkylated with ICH3 in the presence of NaH to provide (VIII).Then,the chiral acyl amino acid (VIII) was coupled to racemic amine (IV) using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide-HCl (EDC) and 7-aza-1-hydroxybenzotriazole (HOAt) to furnish the corresponding amide as a diastereomeric mixture,from which the desired isomer was isolated by reverse phase chromatography.