RPR-130401

Chemical Name: (3aRS,4SR,9SR,9aRS)-2-[2-(2-Methoxyphenyl)-2-propenoyl]-9-(4-methylphenyl)-2,3,3a,4,9,9a-hexahydro-1H-4,9-ethanobenzo[f]isoindole-3a-carboxylic acid
CAS No. 210282-69-2
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:Treatment of 3-oxo-6-phenylcyclohex-1-ene-1-carboxylic acid (I) with methyl iodide and DBU afforded methyl ester (II).Subsequent cycloaddition of (II) with N-n-butoxymethyl-N-(trimethylsilyl)methyl benzylamine (III) in the presence of trifluoroacetic acid gave the octahydroisoindole (IV).Addition of p-tolylmagnesium bromide (V) to the keto group of (IV) produced carbinol (VI),which was converted to the tetracyclic system (VII) by intramolecular cyclization in the presence of trifluoromethanesulfonic acid.Cleavage of the N-benzyl of (VII) group to give (VIII) was effected by transfer hydrogenation with ammonium formate and Pd/C.On the other hand,condensation of (2-methoxyphenyl)acetic acid (IX) with bis(dimethylamino)methane,followed by treatment with acetic anhydride generated the 2-arylpropenoic acid (X),which was converted to acid chloride (XI) employing oxalyl chloride and a catalytic amount of DMF.Coupling of acid chloride (XI) with the tetracyclic amine (VIII) yielded the corresponding amide (XII).The methyl ester group of (XII) was finally hydrolyzed with NaOH to the title carboxylic acid.