KF-27376
Chemical Name: 4-[2-[2-(Dimethylamino)-1-methylethoxy]phenyl]-2,6-dimethyl-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazole-1,3-dione hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III),which is condensed with (R)(+)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the chiral ether derivative (V).The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected chiral propanol derivative (VI),which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII).The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX),which is finally condensed with dimethylamine in hot DMF.
合成路线:The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III),which is condensed with (rac)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the ether derivative (V).The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected propanol derivative (VI),which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII).The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX),which is finally condensed with dimethylamine in hot DMF.
📌 参考资料/链接：
参考文献标题:Pyrrolocarbazole derivs.
文献作者:Ikuina,Y.; Murakata,C.; Saitoh,Y.; Shiotsu,Y.; Iida,T.; Tamaoki,T.; Yamashita,K.; Akinaga,S.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 0768311; US 5728709; WO 9628447
📄 详细内容
合成路线:The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III),which is condensed with (R)(+)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the chiral ether derivative (V).The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected chiral propanol derivative (VI),which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII).The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX),which is finally condensed with dimethylamine in hot DMF.
合成路线:The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III),which is condensed with (rac)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the ether derivative (V).The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected propanol derivative (VI),which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII).The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX),which is finally condensed with dimethylamine in hot DMF.
参考文献标题:Synthesis and structure-activity relationships of pyrrolocarbazole derivatives possessing thrombopoietic activity
文献作者:Ikuina,Y.; et al.
参考来源:217th ACS Natl Meet (March 21 1999,Anaheim) 1999,Abst MEDI 089