bicyclo[3.3.1]nonane-3,7-dione -Drug Synthesis Database

【结构式】

【分子编号】37697

【品名】bicyclo[3.3.1]nonane-3,7-dione

【CA登记号】

【分子式】C₉H₁₂O₂

【分子量】152.19308

【元素组成】C 71.03% H 7.95% O 21.03%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

Condensation of diketone (I) with the organocerium reagent derived from ethylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II), which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N. Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV). This was condensed with 2-amino-4-methylbenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative. Resolution was then achieved by chiral MPLC.

参考文献中间体

合成目标

【1】 Tetrahedron 1996, 51, 16, 5867-80.
【2】 El Achad, R.; Görbig, D.M.; Camps, P.; et al.; Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine - Huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. J Med Chem 1999, 42, 17, 3227.
【3】 Contreras Lascorz, J.; El Achab, R.; Camps Garcia, P.; Baños Diez, J.E.; Muñoz-Torrero Lopez-Ibarra, D.; Badia Sancho, A.; Morral Cardoner, J.; Simon Fornell, M.; Görbig Romeu, M.; Vivas, N.M. (Medichem SA); Polycyclic aminopyridine cpds. which are acetylcholinesterase inhibitors, process for preparing them and their use. EP 0796849; ES 2100129; US 5965569; WO 9713754 .

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)	37697	bicyclo[3.3.1]nonane-3,7-dione		C₉H₁₂O₂	详情	详情
(II)	37698	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]decan-1-ol		C₁₁H₁₈O₂	详情	详情
(III)	37699	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]dec-1-yl methanesulfonate		C₁₂H₂₀O₄S	详情	详情
(IV)	37700	7-ethylbicyclo[3.3.1]non-6-en-3-one		C₁₁H₁₆O	详情	详情
(V)	37701	2-amino-4-methylbenzonitrile	26830-96-6	C₈H₈N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II), which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N. Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV). This was condensed with 2-amino-4-fluorobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative. Resolution was then achieved by chiral MPLC.

参考文献中间体

合成目标

【1】 Tetrahedron 1996, 51, 16, 5867-80.
【2】 El Achad, R.; Görbig, D.M.; Camps, P.; et al.; Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine - Huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. J Med Chem 1999, 42, 17, 3227.
【3】 Contreras Lascorz, J.; El Achab, R.; Camps Garcia, P.; Baños Diez, J.E.; Muñoz-Torrero Lopez-Ibarra, D.; Badia Sancho, A.; Morral Cardoner, J.; Simon Fornell, M.; Görbig Romeu, M.; Vivas, N.M. (Medichem SA); Polycyclic aminopyridine cpds. which are acetylcholinesterase inhibitors, process for preparing them and their use. EP 0796849; ES 2100129; US 5965569; WO 9713754 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	37697	bicyclo[3.3.1]nonane-3,7-dione	C₉H₁₂O₂	详情	详情
(II)	37698	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]decan-1-ol	C₁₁H₁₈O₂	详情	详情
(III)	37699	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]dec-1-yl methanesulfonate	C₁₂H₂₀O₄S	详情	详情
(IV)	37700	7-ethylbicyclo[3.3.1]non-6-en-3-one	C₁₁H₁₆O	详情	详情
(V)	37702	2-amino-4-fluorobenzonitrile	C₇H₅FN₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II), which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N. Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV). This was condensed with 2-aminobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative. Resolution was then achieved by chiral MPLC.

参考文献中间体

合成目标

【1】 Awasthi, S.; Singhal, S.S.; Tetrahedron Asymmetry 1998, 9, 5, 835-849.
【2】 Tetrahedron 1996, 51, 16, 5867-80.
【3】 Muñoz-Torrero, D.; Gorbig, D.M.; Simon, M.; Contreras, J.; Camps, P.; Vivas, N.M.; Badia, A.; Banos, J.E.; Synthesis and evaluation of tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. Bioorg Med Chem 1998, 6, 4, 427-440.
【4】 El Achad, R.; Görbig, D.M.; Camps, P.; et al.; Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine - Huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. J Med Chem 1999, 42, 17, 3227.
【5】 Contreras Lascorz, J.; El Achab, R.; Camps Garcia, P.; Baños Diez, J.E.; Muñoz-Torrero Lopez-Ibarra, D.; Badia Sancho, A.; Morral Cardoner, J.; Simon Fornell, M.; Görbig Romeu, M.; Vivas, N.M. (Medichem SA); Polycyclic aminopyridine cpds. which are acetylcholinesterase inhibitors, process for preparing them and their use. EP 0796849; ES 2100129; US 5965569; WO 9713754 .

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)	37697	bicyclo[3.3.1]nonane-3,7-dione		C₉H₁₂O₂	详情	详情
(II)	37698	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]decan-1-ol		C₁₁H₁₈O₂	详情	详情
(III)	37699	3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]dec-1-yl methanesulfonate		C₁₂H₂₀O₄S	详情	详情
(IV)	37700	7-ethylbicyclo[3.3.1]non-6-en-3-one		C₁₁H₁₆O	详情	详情
(V)	19493	2-aminobenzonitrile	1885-29-6	C₇H₆N₂	详情	详情

Extended Information