FR-161282

Chemical Name: 4'-Methyl-N-[4-[5-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-ylcarbonyl]phenyl]biphenyl-2-carboxamide
CAS No. 168046-41-1, 168046-43-3 (monomesylate salt), 168046-42-2 (sulfate salt(2:1))
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:2-Methoxybenzoic acid (I) was protected as the oxazoline (II).Further coupling with tolylmagnesium bromide,followed by acid hydrolysis of the oxazoline provided the intermediate biphenyl carboxylic acid (III).

合成路线:Condensation of benzodiazepinone (IV) with 4-nitrobenzoyl chloride (V) afforded amide (VI),which was alkylated with ethyl bromoacetate in the presence of NaH to give (VII).The nitro group of (VII) was reduced to aniline (VIII) using Fe and AcOH.Subsequent coupling of (VIII) with the acid chloride generated from biphenyl carboxylic acid (III) and oxalyl chloride produced the corresponding amide (IX).The ester group of (IX) was then hydrolyzed with NaOH,and the resulting carboxylic acid (X) was finally condensed with N-methylpiperazine (XI) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole as the coupling reagents.