1.2.3.5.6.7- Hexahydropyrido quinoxaline-2,3-diones

The lipophilicity (7 m value) and specific hydrophobic surface area of pyrido[l,2-a]pyrazinium-l-olates 342 and -3-olate 343, and l-(4-chlorophe-nyl)-l-hydroxy-l,2-dihydropyrazino[2,l-a]isoquinolinium salt (344) has been measured by reversed-phase thin-layer chromatography (98MI13). Partition coefficient (log/ ) of 9-bromo-5-[(A-phenylaminocarbonyl)-methyl]-l,2,3,5,6,7-hexahydropyrido[l,2,3- fc]quinoxaline-2,3-dione was calculated to be 2.78 (97JMC4053). 

Tetracyclic derivative 317 was obtained from l,2,3,5,6,7-hexahydropyrido[l,2,3- F]quinoxaline-2,5-dione 315 by treatment with (EtO)2P(0)Cl in the presence of KOBu, then with isocyanide 316 in the presence of another portion of KOBu (Scheme 26) <1996JME4654>. 

Depending on the reaction temperature and reaction time, tetrahydroisoquinoline 357 afforded different mixtures of 1,2,3,4,11,11 a-hcxahydro-6//-pyrazino[ 1,2-3]isoquinolines 358-361 and tetracyclic compound 362 (Scheme 30) <2005JA16796>. Each of the individual diastereoisomers 358-361 could be transformed into the compound 362. z7r-3//,4a//-3-Phcnylpcrhydropyra/ino[ 1,2-7]isoquinoline-l,4-dione was prepared via automated parallel solid-phase synthesis on Kaiser oxime resin <1998BML2369>. l,2,3,5,6,7-Hexahydropyrido[l,2,3-r/f ]quinoxaline-2,5-dionc was obtained by catalytic hydrogenation of ethyl 3-(2-oxo-l,2,3,4-tetrahydro-5-quinoxalinyl)acrylate in the presence of TsOH over 5% Pd/C catalyst under 40 psi of hydrogen <1996JME4654>. 

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