合成路线:This compound can be obtained by two related ways:1) The cyclization of 2-formyl-4-methyl-1,2,3,4-tetrahydroisoquinolone-3-carboxylic acid (I) with 2-chloro-5-hydroxy-1,4-naphthoquinone (II) by means of sodium acetate in hot acetic anhydride gives 9-hydroxy-14-methyl-5,8,13,14-tetrahydrobenz[5,6]isoindolo[2,1-b] isoquinoline-8,13-dione (III),which is condensed with dibenzyl phosphonate (IV) by means of N-chlorosuccinimide (NClS) and NaH in benzene to afford (14-methyl-8,13-dioxo-5,8,13,14-tetrahydrobenz[5,6]isoindolo[2,1-b] isoquinolin-9-yl)phosphoric acid dibenzyl ester (V).Finally,this compound is partially hydrolyzed with NaI in refluxing acetone,and the resulting sodium salt treated with aqueous HCl.2) The condensation of 5-hydroxy-1,4-naphthoquinone (VI) with phosphonate (IV) by means of Cl2SO2 followed by a treatment with NaHCO3 gives (1,4-naphthoquinon-5-yl)phosphoric acid dibenzyl ester (VII),which is then cyclized with isoquinoline (I) in hot acetic anhydride to compound (V),already obtained.
参考文献标题:Preparation of 5,8,13,14-tetrahydrobenz(5,6)isoindolo(2,1-b)isoquinolin-8,13-dione derivs
文献作者:Phillips,G.H.; Cowley,B.R.(Glaxo Wellcome plc)
参考来源:EP 0323907
合成路线:This compound can be obtained by two related ways:1) The cyclization of 2-formyl-4-methyl-1,2,3,4-tetrahydroisoquinolone-3-carboxylic acid (I) with 2-chloro-5-hydroxy-1,4-naphthoquinone (II) by means of sodium acetate in hot acetic anhydride gives 9-hydroxy-14-methyl-5,8,13,14-tetrahydrobenz[5,6]isoindolo[2,1-b] isoquinoline-8,13-dione (III),which is condensed with dibenzyl phosphonate (IV) by means of N-chlorosuccinimide (NClS) and NaH in benzene to afford (14-methyl-8,13-dioxo-5,8,13,14-tetrahydrobenz[5,6]isoindolo[2,1-b] isoquinolin-9-yl)phosphoric acid dibenzyl ester (V).Finally,this compound is partially hydrolyzed with NaI in refluxing acetone,and the resulting sodium salt treated with aqueous HCl.2) The condensation of 5-hydroxy-1,4-naphthoquinone (VI) with phosphonate (IV) by means of Cl2SO2 followed by a treatment with NaHCO3 gives (1,4-naphthoquinon-5-yl)phosphoric acid dibenzyl ester (VII),which is then cyclized with isoquinoline (I) in hot acetic anhydride to compound (V),already obtained.
参考文献标题:Fosquidone
文献作者:Castar,J.; Pento,J.T.
参考来源:Drugs Fut 1993,18(10),891
产品链接: CAS No. 114517-02-1›› 产品链接: CAS No.114517-04-3››