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OROS(R)-tacrine, Tacrine hydrochloride, CI-970, THA.HCl, Cognex

9-氨基-1,2,3,4-四氢吖啶盐酸盐水合物 他克林 Chemical Name: 1,2,3,4-Tetrahydroacridin-9-amine hydrochloride
CAS No. 1684-40-8, 321-64-2 (free base)
项目整合开发状态: Launched-1993
项目研究机构: Pfizer (Originator)
合成路线:The cyclocondensation of aniline (VII) with ethyl 2-oxocyclo-hexanecarboxylate (VIII) by means of HCl in refluxing benzene gives 9-acridone (IX),which by treatment with refluxing POCl3 is converted to 9-chloroacridine (X).Finally,this compound is treated with anhydrous NH3 in p-cresol),or with ethanolic ammonia with a Cu catalyst.

合成路线:This compound can be prepared by two different methods:1) By cyclocondensation of p-anisidine (I) with 2-oxocyclohexanecarboxylate (II) to 7-methoxy-1,2,3,4-tetrahydroacridone (III),which by treatment with refluxing POCl3 is converted to 9-chloro-7-methoxy-1,2,3,4-tetrahydroacridine (IV).This compound is converted to final product by treatment with NH3 in refluxing p-cresol.2) By cyclocondensation of 5-methoxyisatin (V) and cyclohexanone (VI) in concentrated aqueous ammonia at 150 C to 7-methoxy-1,2,3,4-tetrahydroacridine-9-carboxamide (VII),followed by a Hoffman degradation with potassium hypobromite.
📌 参考资料/链接:
参考文献标题:7,8,9,10-Tetrahalo-6H-cyclohepta[b]quinolines
文献作者:Sigal,M.V.Jr.; Brent,B.J.; Marchini,P.
参考来源:US 3232945

📄 详细内容


合成路线:By cyclocondensation of 2-aminobenzonitrile (I) with cyclohexanone (II) by means of ZnCl2 at high temperature.

合成路线:By nitration of acridine N-oxide (III) with H2SO4 - HNO3 to the corresponding 9-nitroacridine N-oxide (IV),followed by reduction with Fe - acetic acid.

合成路线:By cyclocondensation of isatine (V) with cyclohexanone (II) and aqueous concentrated NH3 at 150 C in a pressure vessel to acridine-9-carboxamide (VI),followed by a Hoffman degradation with Br2 and sodium methoxide in methanol

合成路线:The cyclocondensation of aniline (VII) with ethyl 2-oxocyclo-hexanecarboxylate (VIII) by means of HCl in refluxing benzene gives 9-acridone (IX),which by treatment with refluxing POCl3 is converted to 9-chloroacridine (X).Finally,this compound is treated with anhydrous NH3 in p-cresol),or with ethanolic ammonia with a Cu catalyst.

参考文献标题:Tacrine
文献作者:Castar,R.M.; Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1987,12(11),1032


合成路线:By cyclocondensation of isatine (V) with cyclohexanone (II) and aqueous concentrated NH3 at 150 C in a pressure vessel to acridine-9-carboxamide (VI),followed by a Hoffman degradation with Br2 and sodium methoxide in methanol

合成路线:This compound can be prepared by two different methods:1) By cyclocondensation of p-anisidine (I) with 2-oxocyclohexanecarboxylate (II) to 7-methoxy-1,2,3,4-tetrahydroacridone (III),which by treatment with refluxing POCl3 is converted to 9-chloro-7-methoxy-1,2,3,4-tetrahydroacridine (IV).This compound is converted to final product by treatment with NH3 in refluxing p-cresol.2) By cyclocondensation of 5-methoxyisatin (V) and cyclohexanone (VI) in concentrated aqueous ammonia at 150 C to 7-methoxy-1,2,3,4-tetrahydroacridine-9-carboxamide (VII),followed by a Hoffman degradation with potassium hypobromite.

参考文献标题:Analogues of 9-amino-1,2,3,4-tetrahydroacridine
文献作者:Bielavsky,J.
参考来源:Coll Czech Chem Commun 1977,422802-7


合成路线:By cyclocondensation of 2-aminobenzonitrile (I) with cyclohexanone (II) by means of ZnCl2 at high temperature.

参考文献标题:
文献作者:Morrison,L.; et al.
参考来源:Tetrahedron Lett 1963,20(4),1277-1281


合成路线:By nitration of acridine N-oxide (III) with H2SO4 - HNO3 to the corresponding 9-nitroacridine N-oxide (IV),followed by reduction with Fe - acetic acid.

参考文献标题:Process for preparing substituted lactones of 2-(2'-hydroxyethyl)nicotinic acid or their N-oxides
文献作者:Klimov,G.A.; Makareva,T.N.; Tilichenko,M.N.; Shepetova,N.M.
参考来源:SU 463323


合成路线:By cyclocondensation of isatine (V) with cyclohexanone (II) and aqueous concentrated NH3 at 150 C in a pressure vessel to acridine-9-carboxamide (VI),followed by a Hoffman degradation with Br2 and sodium methoxide in methanol

参考文献标题:
文献作者:Haslinger,B.; et al.
参考来源:J Chem Listy 1957,51(5),1906


合成路线:By cyclocondensation of isatine (V) with cyclohexanone (II) and aqueous concentrated NH3 at 150 C in a pressure vessel to acridine-9-carboxamide (VI),followed by a Hoffman degradation with Br2 and sodium methoxide in methanol

参考文献标题:
文献作者:Greenspan,S.; et al.
参考来源:J Collect Czech Chem Commun 1958,23(10),1319


产品链接: CAS No. 1684-40-8››

产品链接: CAS No.321-64-2››