Donepezil hydrochloride, BNAG, E-2020, Eranz, Memorit, Memac, Aricept, -Drug Synthesis Database

【结构式】

【药物名称】Donepezil hydrochloride, BNAG, E-2020, Eranz, Memorit, Memac, Aricept

【化学名称】(±)-1-Benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylmethyl)piperidine hydrochloride
　　　　　　(±)-2-(1-Benzyl-4-piperidinylmethyl)-5,6-dimethoxy-1-indanone hydrochloride

【CA登记号】120011-70-3, 123958-79-2 ([2-14C]-labeled), 142057-77-0 (deleted CAS), 120014-06-4 (free base)

【分子式】C₂₄H₃₀ClNO₃

【分子量】415.9646

【开发单位】Eisai (Originator), Natl. Public Health Inst. (Not Determined), Bracco (Licensee), Pfizer (Licensee)

【药理作用】Alzheimer's Dementia, Treatment of , ANALGESIC AND ANESTHETIC DRUGS, Antimigraine Drugs, Attention Deficit Hyperactivity Disorder (ADHD), Treatment of, Autism, Treatment of, Cognition Disorders, Treatment of, Immunologic Neuromuscular Disorders, Treatment of, Migraine, Prophylactic Treatment of, Multiple Sclerosis, Agents for, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Vascular Dementia, Treatment of, Acetylcholinesterase Inhibitors

合成路线1 合成路线2

合成路线1

The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyllithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane - ethyl acetate.

参考文献中间体

【1】 Sugimoto, H.; Tsuchiya, Y.; Higurashi, K.; Karibe, N.; Iimura, Y.; Sasaki, A.; Yamanashi, Y.; Ogura, H.; Araki, S.; Kosasa, T.; Kusota, A.; Kozasa, M.; Yamatsu, K. (Eisai Co., Ltd.); Cyclic amine cpd., its use and pharmaceutical compsns. comprising it. AU 8818216; EP 0296560; EP 0673927; EP 0742207; JP 1989079151; JP 1998067739; US 4895841; US 5100901 .
【2】 Sugimoto, H.; Mishima, M.; Iimura, Y.; Synthesis of 1-benzyl-4-[(5,6-dimethoxy[2-14C]-1-indanon)-2-yl]methylpiperidine hydrochloride (E-2020-14C). J Label Compd Radiopharm 1989, 27, 7, 835-9.
【3】 Castaner, J.; Prous, J.; E-2020. Drugs Fut 1991, 16, 1, 16.

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)	13430	5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one	2107-69-9	C₁₁H₁₂O₃	详情	详情
(II)	13431	1-Benzyl-4-piperidinecarbaldehyde		C₁₃H₁₇NO	详情	详情
(III)	13432	2-[(E)-(1-Benzyl-4-piperidinyl)methylidene]-5,6-dimethoxy-1-indanone	120014-07-5	C₂₄H₂₇NO₃	详情	详情

合成路线2

11C-Labeled donepezil was prepared by methylation of 2-(1-benzylpiperidin-4-ylmethyl)-6-hydroxy-5-methoxyindan-1-one (I) with 11CH3I by means of tetrabutylammonium hydroxide in DMF.

参考文献中间体

【1】 Santens, P.; DeReuck, J.; Dierckx, R.A.; Siegers, G.; Vermeirsch, H.; De Vos, F.; Synthesis of 1-benzyl-4-[(5,[C-11]6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine: A promising ligand for visualisation of acetylcholine esterase by PET. J Label Compd Radiopharm 2000, 43, 6, 595.

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)	43093	2-[(1-benzyl-4-piperidinyl)methyl]-6-hydroxy-5-methoxy-1-indanone		C₂₃H₂₇NO₃	详情	详情

Extended Information