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【结 构 式】

【分子编号】14401

【品名】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

【CA登记号】

【 分 子 式 】C46H57N5O4Si2

【 分 子 量 】800.16088

【元素组成】C 69.05% H 7.18% N 8.75% O 8% Si 7.02%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXX)

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
Extended Information