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

【结构式】

【药物名称】OROS(R)-tacrine, Tacrine hydrochloride, CI-970, THA.HCl, Cognex

【化学名称】1,2,3,4-Tetrahydroacridin-9-amine hydrochloride

【CA登记号】1684-40-8, 321-64-2 (free base)

【分子式】C₁₃H₁₅ClN₂

【分子量】234.7309

【开发单位】Pfizer (Originator)

【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Acetylcholinesterase Inhibitors, Butyrylcholinesterase Inhibitors

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

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

参考文献中间体

【1】 Morrison, L.; et al.; Tetrahedron Lett 1963, 20, 4, 1277-1281.
【2】 Castaner, R.M.; Serradell, M.N.; Castaner, J.; Tacrine. Drugs Fut 1987, 12, 11, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	19493	2-aminobenzonitrile	1885-29-6	C₇H₆N₂	详情	详情
(II)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情

合成路线2

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.

参考文献中间体

【1】 Klimov, G.A.; Makareva, T.N.; Tilichenko, M.N.; Shepetova, N.M.; Process for preparing substituted lactones of 2-(2'-hydroxyethyl)nicotinic acid or their N-oxides. SU 463323 .
【2】 Castaner, R.M.; Serradell, M.N.; Castaner, J.; Tacrine. Drugs Fut 1987, 12, 11, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	28177	1,2,3,4-tetrahydro-10-acridiniumolate		C₁₃H₁₃NO	详情	详情
(IV)	28178	9-nitro-1,2,3,4-tetrahydro-10-acridiniumolate		C₁₃H₁₂N₂O₃	详情	详情

合成路线3

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

参考文献中间体

【1】 Haslinger, B.; et al.; J Chem Listy 1957, 51, 5, 1906.
【2】 Greenspan, S.; et al.; J Collect Czech Chem Commun 1958, 23, 10, 1319.
【3】 Bielavsky, J.; Analogues of 9-amino-1,2,3,4-tetrahydroacridine. Coll Czech Chem Commun 1977, 42, 2802-7.
【4】 Castaner, R.M.; Serradell, M.N.; Castaner, J.; Tacrine. Drugs Fut 1987, 12, 11, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情
(V)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(VI)	28179	1,2,3,4-tetrahydro-9-acridinecarboxamide		C₁₄H₁₄N₂O	详情	详情

合成路线4

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.

参考文献中间体

【1】 Hottelart, C.; et al.; J Chem Soc 1947, 92, 3, 634-637.
【2】 Sigal, M.V. Jr.; Brent, B.J.; Marchini, P.; 7,8,9,10-Tetrahalo-6H-cyclohepta[b]quinolines. US 3232945 .
【3】 Castaner, R.M.; Serradell, M.N.; Castaner, J.; Tacrine. Drugs Fut 1987, 12, 11, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(VIII)	11889	ethyl 2-oxocyclohexanecarboxylate; Ethyl 2-cyclohexanonecarboxylate	1655-07-8	C₉H₁₄O₃	详情	详情
(IX)	28180	1,3,4,4a,9a,10-hexahydro-9(2H)-acridinone		C₁₃H₁₅NO	详情	详情
(X)	28181	9-chloro-1,2,3,4-tetrahydroacridine		C₁₃H₁₂ClN	详情	详情

Extended Information