【结 构 式】 |
【分子编号】14425 【品名】2,5-diamino-6-[[(1R,2R,3S)-2,3-bis(hydroxymethyl)cyclobutyl]amino]-4-pyrimidinol 【CA登记号】 |
【 分 子 式 】C10H17N5O3 【 分 子 量 】255.27688 【元素组成】C 47.05% H 6.71% N 27.43% O 18.8% |
合成路线1
该中间体在本合成路线中的序号:(LV)6) The stereoselective cyclization of bis[(-)-menthyl] fumarate (XLVII) with 1,1-bis(methylsulfanyl)ethylene (XX) by means of diisobutylaluminum chloride in hexane gives (1S-trans)-3,3-bis(methylsulfanyl)cyclobutane-1,2-dicarboxylic acid di-(-)-menthyl ester (XLVIII), which is reduced with LiAlH4 in THF yielding (1S-trans)-3,3-bis(methylsulfanyl)cyclobutane-1,2-dimethanol (XXIV). The silylation of (XXIV) with tert-butyldimethylsilyl chloride (TBMS-Cl) and imidazole in DMF affords the bis-silylated diol (II), which is treated with AgNO3 and N-chlorosuccinimide (NCS) in acetonitrile/water to give the cyclobutanone (L). The reaction of (L) with O-methylhydroxylamine in pyridine yields the corresponding O-methyloxime (LI), which is selectively reduced with NaBH4 in THF to the cyclobutylamine (LII). The condensation of (LII) with 4-chloro-6-hydroxy-5-nitropyrimidine-2-amine (LIII) by means of triethylamine in DMF affords the substituted 5-nitro-2,4-diaminopyrimidine (LIV), which is reduced with H2 over Pd/C in formic acid yielding the corresponding triaminopyrimidine (LV). Finally, this compound, without isolation, is cyclized with formic acid at 130 C.
【1】 Ireland, C.; Leeson, P.A.; Castaner, J.; Lobucavir. Drugs Fut 1997, 22, 4, 359. |
【2】 Pariza, R.J.; Hannick, S.M.; Sowin, T.J.; Doherty, E.M. (Bristol-Myers Squibb Co.); Process for preparing substd. Cyclobutanes. US 5399775 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IL) | 14419 | tert-butyl(dimethyl)silyl [(1S,2S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,3-bis(methylsulfanyl)cyclobutyl]methyl ether; tert-butyl[[(1S,4S)-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2,2-bis(methylsulfanyl)cyclobutyl]methoxy]dimethylsilane | C20H44O2S2Si2 | 详情 | 详情 | |
(XLVII) | 14417 | bis[(1R,2S,4S)-2-isopropyl-4-methylcyclohexyl] (E)-2-butenedioate | C24H40O4 | 详情 | 详情 | |
(XLVIII) | 14418 | bis[(1R,2S,4S)-2-isopropyl-4-methylcyclohexyl] (1S,2S)-3,3-bis(methylsulfanyl)-1,2-cyclobutanedicarboxylate | C28H48O4S2 | 详情 | 详情 | |
(L) | 14420 | (2S,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutanone | C18H38O3Si2 | 详情 | 详情 | |
(LI) | 14421 | (2R,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutanone O-methyloxime | C19H41NO3Si2 | 详情 | 详情 | |
(LII) | 14422 | (1R,2R,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutanamine; (1R,2R,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutylamine | C18H41NO2Si2 | 详情 | 详情 | |
(LIII) | 14423 | 2-amino-6-chloro-5-nitro-4-pyrimidinol | C4H3ClN4O3 | 详情 | 详情 | |
(LIV) | 14424 | 2-amino-6-[[(1R,2R,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutyl]amino]-5-nitro-4-pyrimidinol | C22H43N5O5Si2 | 详情 | 详情 | |
(LV) | 14425 | 2,5-diamino-6-[[(1R,2R,3S)-2,3-bis(hydroxymethyl)cyclobutyl]amino]-4-pyrimidinol | C10H17N5O3 | 详情 | 详情 |