【结 构 式】 |
【分子编号】14390 【品名】methyl (E)-4-oxo-4-(2-oxo-1,3-oxazolan-3-yl)-2-butenoate 【CA登记号】 |
【 分 子 式 】C8H9NO5 【 分 子 量 】199.1632 【元素组成】C 48.25% H 4.55% N 7.03% O 40.17% |
合成路线1
该中间体在本合成路线中的序号:(XIX)3) The stereocontrolled cyclization of (E)-3-(2-oxooxazolidin-3-ylcarbonyl)-2-propenoic acid methyl ester (XIX) with 1,1-di(methylsulfanyl)ethylene (XX) catalyzed by a chiral reagent prepared in situ with diisopropoxytitanium dichloride and the chiral dioxolane (XXI), gives [1S-(1alpha,2beta)]-3,3-bis(methylsulfanyl)-2-(2-oxooxazolidin-3-ylcarbonyl)cyclobutane-1-carboxylic acid methyl ester (XXII), which is treated with magnesium methoxide in methanol yielding the dicarboxylic ester (XXIII). The reduction of (XXIII) with LiAlH4 in ether affords the corresponding dimethanol compound (XXIV), which is silylated with tert-butyldiphenylsilyl chloride (BPS-Cl), triethylamine and 4-(dimethylamino)pyridine (DMAP) in dichloromethane giving the bis(silyl) ether (XXV). The reaction of (XXV) with N-chlorosuccinimide (NCS) and AgNO3 in acetonitrile/water yields the cyclobutanone (XXVI), which is reduced with diisobutylaluminum hydride (DIBAL) in toluene affording the silylated [1S-(1alpha,2beta,3beta)]-3-hydroxycyclobutyl-1,2-dimethanol (XXVII). The reaction of (XXVII) with methanesulfonyl chloride and triethylamine gives the expected mesylate (XXVIII), which is condensed with 6-O-(2-methoxyethyl)guanine (XXIX) by means of LiH in DMF to afford the corresponding adduct (XXX). Finally, this compound is deprotected by treatment with HCl in methanol.
【2】 Ichikawa, Y.-I.; Narita, A.; Matsuo, K.; Aoyama, K.; Matsumura, F.; Nishiyama, Y.; Matsubara, K.; Nagahata, T.; Hoshino, H.; Seki, J.-i.; Narasaka, K.; Hayashi, Y. (Nippon Kayaku Co., Ltd.); Novel cyclobutane derivative and process for producing same. EP 0358154; JP 1991095165; JP 1995149718; JP 1996301765; JP 1996301766; WO 9005730 . |
【3】 Ichikawa, Y.; Narita, A.; Shiozawa, A.; Hayashi, Y.; Narasaka, K.; Enantio- and diastereo-selective synthesis of carbocyclic oxetanocin analogues. J Chem Soc Chem Commun 1989, 24, 24, 1919-21. |
【1】 Ireland, C.; Leeson, P.A.; Castaner, J.; Lobucavir. Drugs Fut 1997, 22, 4, 359. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XIX) | 14390 | methyl (E)-4-oxo-4-(2-oxo-1,3-oxazolan-3-yl)-2-butenoate | C8H9NO5 | 详情 | 详情 | |
(XX) | 14391 | 1,1-bis(methylsulfanyl)ethylene; methyl 1-(methylsulfanyl)vinyl sulfide | 51102-74-0 | C4H8S2 | 详情 | 详情 |
(XXI) | 14392 | [(4S,5S)-5-[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl](diphenyl)methanol | 93379-48-7 | C31H30O4 | 详情 | 详情 |
(XXII) | 14393 | methyl (1S,2S)-3,3-bis(methylsulfanyl)-2-[(2-oxo-1,3-oxazolan-3-yl)carbonyl]cyclobutanecarboxylate | C12H17NO5S2 | 详情 | 详情 | |
(XXIII) | 14394 | dimethyl (1S,2S)-3,3-bis(methylsulfanyl)-1,2-cyclobutanedicarboxylate | C10H16O4S2 | 详情 | 详情 | |
(XXIV) | 14395 | [(1S,4S)-4-(hydroxymethyl)-2,2-bis(methylsulfanyl)cyclobutyl]methanol | C8H16O2S2 | 详情 | 详情 | |
(XXV) | 14396 | tert-butyl(diphenyl)silyl [(1S,2S)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3,3-bis(methylsulfanyl)cyclobutyl]methyl ether; tert-butyl[[(1S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,2-bis(methylsulfanyl)cyclobutyl]methoxy]diphenylsilane | C40H52O2S2Si2 | 详情 | 详情 | |
(XXVI) | 14397 | (2S,3S)-2,3-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)cyclobutanone | C38H46O3Si2 | 详情 | 详情 | |
(XXVII) | 14398 | (1S,2S,3S)-2,3-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)cyclobutanol | C38H48O3Si2 | 详情 | 详情 | |
(XXVIII) | 14399 | tert-butyl[((1S,2S,4S)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]cyclobutyl)methoxy]diphenylsilane; tert-butyl(diphenyl)silyl ((1S,2S,3S)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]cyclobutyl)methyl ether | C41H54O3SSi2 | 详情 | 详情 | |
(XXIX) | 14400 | 6-(2-methoxyethoxy)-9H-purin-2-amine; 6-(2-methoxyethoxy)-9H-purin-2-ylamine | C8H11N5O2 | 详情 | 详情 | |
(XXX) | 14401 | 9-[(1R,2R,3S)-2,3-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)cyclobutyl]-6-(2-methoxyethoxy)-9H-purin-2-amine; 9-[(1R,2R,3S)-2,3-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)cyclobutyl]-6-(2-methoxyethoxy)-9H-purin-2-ylamine | C46H57N5O4Si2 | 详情 | 详情 |