新产品编号:467199
Chemical Name: 4-(3-Bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-N1-cyclohexyl-N2-[3-(1H-imidazol-1-yl)propyl]piperazine-1,2(R)-dicarboxamide isomer B
CAS No. 218792-48-4 (undefined stereoch.)
项目整合开发状态: Biological Testing
项目研究机构: Pharmacopeia (Originator), Schering-Plough (Originator)
合成路线:(R)-Piperazine-2-carboxylic acid (I) is sequentially protected with Boc-ON as the 4-Boc piperazine (II) and then with Fmoc-Cl to afford the 1-Fmoc-4-Boc-piperazine (III).Subsequent coupling of the protected piperazinecarboxylic acid (III) with 1-(3-aminopropyl)imidazole (IV) furnishes amide (V).The N-Fmoc group of (V) is selectively removed with piperidine in THF to provide amine (VI),which is further coupled with cyclohexyl isocyanate (VII),yielding urea (VIII).Then,the N-Boc protecting group of (VIII) is cleaved by means of trifluoroacetic acid to give (IX).Finally,condensation of piperazine (IX) with the tricyclic alkyl chloride (X) in the presence of 1,2,2,6,6-pentamethylpiperidine generates the title compound.(1,2)
📌 参考资料/链接：
参考文献标题:Benzpyrido cycloheptane cpds.useful for inhibition of farnesyl protein transferase
文献作者:Baldwin,J.J.; Cooper,A.B.; Girijavallabhan,V.M.; Ganguly,A.; Reader,J.C.; Huang,C.(Pharmacopeia,Inc.; Schering Corp.)
参考来源:EP 0989983; JP 2002504144; WO 9857960
📄 详细内容
合成路线:(R)-Piperazine-2-carboxylic acid (I) is sequentially protected with Boc-ON as the 4-Boc piperazine (II) and then with Fmoc-Cl to afford the 1-Fmoc-4-Boc-piperazine (III).Subsequent coupling of the protected piperazinecarboxylic acid (III) with 1-(3-aminopropyl)imidazole (IV) furnishes amide (V).The N-Fmoc group of (V) is selectively removed with piperidine in THF to provide amine (VI),which is further coupled with cyclohexyl isocyanate (VII),yielding urea (VIII).Then,the N-Boc protecting group of (VIII) is cleaved by means of trifluoroacetic acid to give (IX).Finally,condensation of piperazine (IX) with the tricyclic alkyl chloride (X) in the presence of 1,2,2,6,6-pentamethylpiperidine generates the title compound.(1,2)
参考文献标题:Structural optimization of a farnesyl protein transferase inhibitor derived from a small molecule combinatorial library
文献作者:Huang,C.-Y.; Rokosz,L.L.; Stauffer,T.M.; Huang,H.; Li,G.; Reader,J.C.; Baldwin,J.J.
参考来源:225th ACS Natl Meet (March 23 2003,New Orleans) 2003,Abst MEDI 131