tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】41239

【品名】tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₁H₂₀INO₂

【分子量】325.18981

【元素组成】C 40.63% H 6.2% I 39.02% N 4.31% O 9.84%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The Friedel Crafts condensation of 6-methoxyindolin-2-one (I) with acetyl chloride and AlCl3 gives the 5-acetyl-6-methoxyindolin-2-one (II), which is treated with hydroxylamine and acetic anhydride to yield the O-acetyloxime (III). The cyclization of (III) affords the 3-methyl-6,7-dihydro-5H-isoxazolo[4,5-f]indol-6-one (IV), which is condensed with 4-(iodomethyl)piperidine-1-carboxylic acid tert-butyl ester (V) to provide the adduct (VI). Finally this compound is deprotected with TFA and benzylated with benzyl bromide (VII) to furnish the target compound.

参考文献中间体

合成目标

【1】 Maggi, A.; Brufani, M.; Lappa, S.; Filocamo, L.; New acetylcholinesterease inhibitors. Drugs Fut 1997, 22, 4, 397.
【2】 Villalobos, A.; et al.; 5, 7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxaxol-6-one: A potent and centrally-selective inhibitor of acetylcholinesterase with an improved margin of safety. J Med Chem 1995, 38, 15, 2802.

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)	41235	6-methoxy-1,3-dihydro-2H-indol-2-one		C₉H₉NO₂	详情	详情
(II)	41236	5-acetyl-6-hydroxy-1,3-dihydro-2H-indol-2-one		C₁₀H₉NO₃	详情	详情
(III)	41237	5-ethanimidoyl-6-hydroxy-1,3-dihydro-2H-indol-2-one		C₁₂H₁₂N₂O₄	详情	详情
(IV)	41238	3-methyl-5,7-dihydro-6H-isoxazolo[4,5-f]indol-6-one		C₁₀H₈N₂O₂	详情	详情
(V)	41239	tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate		C₁₁H₂₀INO₂	详情	详情
(VI)	41240	tert-butyl 4-[2-(6-oxo-6,7-dihydro-5H-isoxazolo[4,5-f]indol-3-yl)ethyl]-1-piperidinecarboxylate		C₂₁H₂₇N₃O₄	详情	详情
(VII)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

4-(Hydroxymethyl)piperidine (XVIII) is protected as the N-Boc derivative (XIX) with Boc2O in CH2Cl2. Conversion of alcohol (XIX) into the corresponding mesylate, followed by treatment with NaI in acetone, furnishes the alkyl iodide (XX). Quaternization of triphenylphosphine with iodide (XX) in refluxing acetonitrile gives rise to the phosphonium salt (XXI).

参考文献中间体

合成目标

【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Rosauer, K. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6265434; WO 0059503 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVIII)	32954	4-piperidinylmethanol	C₆H₁₃NO	详情	详情
(XIX)	40399	tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate	C₁₁H₂₁NO₃	详情	详情
(XX)	41239	tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate	C₁₁H₂₀INO₂	详情	详情
(XXI)	65138	{[1-(tert-butoxycarbonyl)-4-piperidinyl]methyl}(triphenyl)phosphonium iodide	C₂₉H₃₅INO₂P	详情	详情

Extended Information