SCH-226374

Chemical Name: 4-[8-Chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(S)-yl]-2(R)-[N-benzyl-N-[3-(4-methyl-1H-imidazol-1-yl)propyl]carbamoyl]piperazine-1-carboxylic acid cyclohexyl ester
CAS No. 279233-71-5
项目整合开发状态: Preclinical
项目研究机构: Pharmacopeia (Originator), Schering-Plough (Originator)
合成路线:The alkylation of 4-methylimidazole (I) with N-(3-bromopropyl)phthalimide (II) produced a mixture of N-alkylated regioisomers (III) and (IV).After selective derivatization of the undesired 5-methyl isomer (III) with trityl chloride,the 4-methyl derivative was isolated by flash chromatography and subsequently subjected to phthaloyl group hydrazinolysis to yield amine (V).Reductive condensation of amine (V) with benzaldehyde (VI) in the presence of NaBH4 afforded the N-benzyl amine (VII).

合成路线:(R)-Piperazine-2-carboxylic acid,obtained by resolution of the racemic piperazine (VIII) with (-)-camphorsulfonic acid,was regioselectively protected with Boc-ON at the 4-N atom,yielding the tert-butyl carbamate (IX).Subsequent treatment with cyclohexyl chloroformate (X) produced the bis-carbamate (XI),which was further subjected to selective Boc group cleavage under acidic conditions.The resultant piperazine (XII) was condensed with the tricyclic alkyl chloride (XIII),producing a diastereomeric mixture of N-alkylated adducts from which the required isomer (XIV) was isolated by flash chromatography.Finally,coupling of acid (XIV) with the intermediate amine (VII) by means of EDC and HOBt gave rise to the title compound.