1-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】11612

【品名】1-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone

【CA登记号】

【分子式】C₁₃H₁₆O

【分子量】188.26944

【元素组成】C 82.94% H 8.57% O 8.5%

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)

This compound can be obtained in two different ways: 1) The bromination of 1-(2-ethylindan-2-yl)-1-ethanone (I) with Br2 in ether gives 2-bromo-1-(2-ethylindan-2-yl)-1-ethanone (II), which is then cyclized with formamide by heating at 170-80 C. 2) The cyclization of alpha,alpha'-dibromo-o-xylene (III) with 4-penten-2-one (IV) by means of tetrabutylammonium hydroxide in toluene at 100 C gives 1-(2-vinylindan-2-yl)-1-ethanone (V), which is brominated with Br2 in dichloromethane to yield 2-bromo-1-(2-vinylindan-2-yl)-1-ethanone (VI). The cyclization of (VI) with formamide at 160 C as before affords 4-(2-vinylindan-2-yl)-1H-imidazole (VII), which is finally hydrogenated with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Graziano, M.P.; Maxham, C.P.; Malbon, C.C.; Purified rat hepatic beta2-adrenergic receptor: Structural similarities in the rat fat cell beta1-adrenergic receptor. J Biol Chem 1985, 260, 7665-74.
【2】 Karjalainen, A.L.; Karjalainen, A.J. (Orion Pharma); 4(5)-Substd. imidazole derivs., and intermediates and processes for their preparation. EP 0247764; US 4933359 .
【3】 Karjalainen, A.J.; Virtanen, R.E.; Kurkela, K.O.A.; Karjalainen, A. (Orion Pharma); Substd. imidazole derivs. and their preparation and use. AU 8550083; EP 0183492; EP 0310745; ES 8704462; ES 8801248; GB 2167408; JP 1986143366 .
【4】 Prous, J.; Castaner, J.; Atipamezole. Drugs Fut 1990, 15, 5, 448.

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)	11612	1-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₆O	详情	详情
(II)	11613	2-Bromo-1-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₅BrO	详情	详情
(III)	11614	1,2-Bis(bromomethyl)benzene; alpha,alpha'-Dibromo-o-xylene	91-13-4	C₈H₈Br₂	详情	详情
(IV)	11615	4-Penten-2-one		C₅H₈O	详情	详情
(V)	11616	1-(2-Vinyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₄O	详情	详情
(VI)	11617	2-Bromo-1-(2-vinyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₃BrO	详情	详情
(VII)	11618	4-(2-Vinyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole		C₁₄H₁₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

A new synthesis of atipamezole has been described: The cyclization of alpha,alpha'-dibromo-o-xylene (I) with acetylacetone (II) by means of NaOH and tetrabutylammonium bromide in toluene/water at 80 C under phase-transfer conditions gives the unstable diacetyl derivative (III), which presumably undergoes cleavage to afford 2-acetylindane (IV). The alkylation of (IV) with ethyl iodide and potassium tert-butoxide yields 2-acetyl-2-ethylindane (V), which is brominated with Br2 to give 2-(bromoacetyl)-2-ethylindane (VI). Finally, this compound is cyclized with formamide at 160 C [some 2-ethyl-2-(4-oxazolyl)indane is also formed but is easily eliminated]; the cyclization can also be carried out with formamidine in liquid ammonia.

参考文献中间体

合成目标

【1】 Wong, W.C.; Gluchowski, C.; A concise synthesis of atipamezole. Synthesis 1995, 2, 2, 139.

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)	11619	2,2-Bis(bromomethyl)indane		C₁₁H₁₂Br₂	详情	详情
(II)	11620	2,4-Pentanedione;acetylacetone	123-54-6	C₅H₈O₂	详情	详情
(III)	11621	1-(2-Acetyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₄O₂	详情	详情
(IV)	11622	1-(2,3-Dihydro-1H-inden-2-yl)-1-ethanone		C₁₁H₁₂O	详情	详情
(V)	11612	1-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₆O	详情	详情
(VI)	11613	2-Bromo-1-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone		C₁₃H₁₅BrO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

The alkylation of indane-2-carboxylic acid methyl ester (I) with ethyl iodide by means of lithium isopropylcyclohexylamide (LiICA) in THF/DMSO gives the 2-ethyl substituted compound (II), which is hydrolyzed with tBu-OK in DMSO, yielding 2-ethylindane-2-carboxylic acid (III). The reaction of (III) with methanesulfonyl chloride and diazomethane affords the alpha-diazoketone (IV), which is treated with dimethyldioxirane (DMDO) in acetone to provide the ketoaldehyde (V). Finally, this compound is cyclized with 11C-formaldehyde and NH4OH by means of ZnO in THF/water to yield the target labeled imidazole derivative. The intermediate ketoaldehyde (V) has also been obtained in two other ways: a) The alkylation of 2-(diethoxyacetyl)indane (VI) with ethyl iodide by means of tBu-OK in THF gives the corresponding 2-ethyl-substituted compound (VII), which is finally hydrolyzed to the desired ketoaldehyde (V) with HCl in THF/water. b) The oxidation of 2-acetyl-2-ethylindane (VIII) with SeO2 in hot acetic acid/water gives also the desired ketoaldehyde (V).

参考文献中间体

合成目标

【1】 Roeda, D.; et al.; Synthesis of [11C]atipamezole, a potential PET ligand for the alpha2-adrenergic receptor in the brain. J Label Compd Radiopharm 2002, 45, 1, 37.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	54919	methyl 2-indanecarboxylate	C₁₁H₁₂O₂	详情	详情
(II)	54920	methyl 2-ethyl-2-indanecarboxylate	C₁₃H₁₆O₂	详情	详情
(III)	54921	2-ethyl-2-indanecarboxylic acid	C₁₂H₁₄O₂	详情	详情
(IV)	54922		C₁₃H₁₄N₂O	详情	详情
(V)	54923	2-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-2-oxoacetaldehyde	C₁₃H₁₄O₂	详情	详情
(VI)	54924	1-(2,3-dihydro-1H-inden-2-yl)-2,2-diethoxy-1-ethanone	C₁₅H₂₀O₃	详情	详情
(VII)	54925	1-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2-dimethoxy-1-ethanone	C₁₅H₂₀O₃	详情	详情
(VIII)	11612	1-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1-ethanone	C₁₃H₁₆O	详情	详情

Extended Information