CGP-62198A
Chemical Name: (2S,4S,5S,7S)-N-[7-[[2-(1-Acetyl-4-piperidinyl)ethyl]carbamoyl]-4-amino-5-hydroxy-2-isopropyl-8-methylnonyl]-2-(4-methoxybutoxy)benzamide; (2S,4S,5S,7S)-N-[2-(1-Acetylpiperidin-4-yl)ethyl]-5-amino-4-hydroxy-2,7-diisopropyl-8-[2-(4-methoxybutoxy)benzamido]octanamide
CAS No. 180183-51-1, 179995-88-1 (monoHCl)
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:The simultaneous reduction of the carboxylic and azido groups of 3-azidobutyric acid derivative (I) first with ethoxalyl chloride and NaBH4 and then with H2 over Pd/C in gives the 4-aminobutanol derivative (II),which is protected at the amino group with tert-butoxycarbonyl anhydride providing carbamate (III).The reaction of the OH group of (III) first with methanesulfonyl chloride and then with sodium azide affords the primary azide (IV),which is reduced with H2 over Pd/C to the primary amine (V).The acylation of (V) with 2-(4-methoxybutoxy)benzoic acid (VI) by means of BOP-Cl gives the benzamide (VII),which is condensed at the lactone group with 2-(1-acetylpiperidin-4-yl)ethylamine (VIII) by heating at 80 C to afford intermediate (IX) with a new amide group.Finally,the carbamate protecting group of (IX) is hydrolyzed with HCl in dioxane.
📌 参考资料/链接：
参考文献标题:Aromatically substituted omega -amino-alkanoic acid amides and alkanoic acid diamides
文献作者:Maibaum,J.K.; et al.(Novartis AG)
参考来源:CA 2164571; EP 0716077
📄 详细内容
合成路线:The simultaneous reduction of the carboxylic and azido groups of 3-azidobutyric acid derivative (I) first with ethoxalyl chloride and NaBH4 and then with H2 over Pd/C in gives the 4-aminobutanol derivative (II),which is protected at the amino group with tert-butoxycarbonyl anhydride providing carbamate (III).The reaction of the OH group of (III) first with methanesulfonyl chloride and then with sodium azide affords the primary azide (IV),which is reduced with H2 over Pd/C to the primary amine (V).The acylation of (V) with 2-(4-methoxybutoxy)benzoic acid (VI) by means of BOP-Cl gives the benzamide (VII),which is condensed at the lactone group with 2-(1-acetylpiperidin-4-yl)ethylamine (VIII) by heating at 80 C to afford intermediate (IX) with a new amide group.Finally,the carbamate protecting group of (IX) is hydrolyzed with HCl in dioxane.
参考文献标题:Design and synthesis of novel,fully non-peptide transition state mimetic renin inhibitors bearing an O-alkyl substituted salicylamide (P3SP-P3)-moiety with high oral in vivo potency
文献作者:Maibaum,J.; et al.
参考来源:15th EFMC Int Symp Med Chem (Sept 6 1998,Edinburgh) 1998,Abst P.231