新产品编号:301089
Chemical Name: 5-(Acetamido)-N-[2-[1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-ylcarbonyl]-1H-indol-5-yl]-1H-indole-2-carboxamide
CAS No. 199806-33-2
项目整合开发状态: Preclinical
项目研究机构: Panorama Research (Originator)
合成路线:Treatment of the cyclopropabenzindole derivative (CBI) (I) with hydrochloric acid in ethyl acetate affords the chloromethyl derivative (II).The final step is the condensation of (II) with the acid (VIII) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) in DMF.The acid (VIII) was prepared as follows: Ethyl 5-nitroindole-2-carboxylate (III) is reductively transformed to its corresponding amine (IV) by hydrogenation over Pd/C.The amine (IV) is then converted to its acetamido ester (V) by treatment with acetic anhydride in ethyl acetate.Ester (V) is then hydrolyzed using NaOH to afford the corresponding acid (VI),which is coupled to amine (IV) in the presence of EDCI to yield ester (VII).Finally (VII) is converted to acid (VIII) by treatment with NaOH.
📌 参考资料/链接：
参考文献标题:DNA-binding indole derivs.,their prodrugs and immunoconjugates as anticancer agents
文献作者:Larrick,J.W.; Wright,S.C.; Wang,Y.(Panorama Research,Inc.)
参考来源:WO 9744000
📄 详细内容
合成路线:Treatment of the cyclopropabenzindole derivative (CBI) (I) with hydrochloric acid in ethyl acetate affords the chloromethyl derivative (II).The final step is the condensation of (II) with the acid (VIII) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) in DMF.The acid (VIII) was prepared as follows: Ethyl 5-nitroindole-2-carboxylate (III) is reductively transformed to its corresponding amine (IV) by hydrogenation over Pd/C.The amine (IV) is then converted to its acetamido ester (V) by treatment with acetic anhydride in ethyl acetate.Ester (V) is then hydrolyzed using NaOH to afford the corresponding acid (VI),which is coupled to amine (IV) in the presence of EDCI to yield ester (VII).Finally (VII) is converted to acid (VIII) by treatment with NaOH.
参考文献标题:Synthesis and preliminary biological evaluations of CC-1065 analogues: Effects of different linkers terminal amides on biological activity
文献作者:Wang,Y.; Yuan,H.; Ye,W.; Wright,S.C.; Wang,H.; Larrick,J.W.
参考来源:J Med Chem 2000,43(8),1541