8//-Pyrido quinoxalin-8-ones

Treatment of bis-lactim ether 420 with BuLi, then with cw-l,4-dichloro-2-butene in the presence of Nal afforded 3,4,9,9n-tetrahydro-6//-pyrido[l,2-fl]pyrazin-4-one (421) with 96% diastereomeric excess (97TA1855). Reaction of l,2-diphenyl-6-methyl-quinoxaline with 1,4-dichlorobutane in THF in the presence of Na at —78°C afforded a 3 1 mixture of 4a,5-diphenyl-9-methyl-l,2,3,4-tetrahydro-4a//-pyrido[l,2-n]quinoxaline and 4-(4-chlorobutyl)-2,3-diphenyl-6-methyl-1,4-dihydroquinoxaline (98JHC1349). 

Thermolysis of 3-alkyloxy- and 3-aroyloxy-5-phenyl-l,2,4-pyrrolo[l,2- ]quinoxaline-l,2,4-triones afforded 5-phenyl-9-(4-phenyl-3-oxo-3,4-dihydro-2-quinoxalinyl)-6,8,10-trioxo-5,6,9,10-tetrahydro-87/-pyrido[l,2-tf ]quinoxaline-7,9-dicarboxylates <2000CHE615, 2004CHE1295> and 7-aroyl-8-aroyloxy-5-phenyl-9-(4-phenyl-3-oxo-3,4-dihydro-2-quinoxalinyl)-5,6-dihydro-1077-pyrido[l,2- ]quinoxaline-6,10-diones <2002CHE498>, respectively. Thermolysis of 3-aryl-2-(5-aryl-2,3-dioxo-2,3-dioxo-4-furanyl)quinoxalines gave 7-aroyl-8-aroyloxy-6-aryl-9-(3-aryl-2-quinoxalyl)-10/7-pyrido[l,2- ]quinoxalin-10-ones <2001CHE1314, 2002RCB850>. 

Reaction of 2-aminopyridine and 3-(jV, Af-dimethylaminocarbony 1) furo[2,3-6]quinoxaline 69 in boiling butanol gave 2-(2-oxo-2//-pyrido [ 1,2-a]pyrimidin-3-yl)-3,4-dihydroquinoxalin-2-one 70 (80CPB3537). 

The oxidation of quinoxaline derivatives of 2//-pyrido[l, 2-a]pyrimidin-2-one 70 and 291 with 30% hydrogen peroxide in acetic acid at 100°C gave 2,3-dioxo-l,2,3,4-tetrahydroquinoxaline 292 in good yield (80CPB3537). 

Chloro derivative 291 was obtained from dioxo derivative 70 by treatment of phosphoryl chloride in dimethylformamide at 100°C for 2 hours (80CPB3537). The treatment of chloro derivative 291 with methylhydra-zine in a mixture of ethanol and chloroform under reflux gave 2H-pyrido[ 1,2-a]pyrimidin-2-one 295 and rearranged pyridazino[3,4-6]-quinoxaline 296 in 4.8% and 78% yields, respectively (Scheme 21) (80CPB3537). 3,4-Dihydroquinoxalinone 70 could not be rearranged into pyridazino[3,4-6]quinoxaline 296 by treatment with methylhydrazine. When hydrazine hydrate was employed instead of methylhydrazine, tricyclic ethyl ester 297 (R1 = Et) was obtained. The latter reaction gave methyl ester 297 (R1 = Me) when carried out in a mixture of methanol and chloroform (80CPB3537). 

The treatment of a ferf-butoxycarbonylamino group present in a side chain of 6,7-dihydro-3H,5H-pyrido[l,2,3-cfe]quinoxalin-3-one with 4N HC1 in a dioxane liberated amino group, which was reductively alkylated using heteroaromatic aldehydes followed by the treatment of the formed Schiff bases with NaB(OAc)3H (08WOP2008/003690). 

Copper-catalyzed coupling reaction of 2-bromoanilines and pipecoli-nic acid provided 6,6fl,7,8,9,10-hexahydro-5H-pyrido[l,2-a]quinoxalin-6-ones 392 (09BML4119). Using [Pd(r/3-C3H5)Cl2]2 with (2-biphenyl)di-ferf-butylphosphine catalyst system and Cu(I)Br gave lower yields. 

Oxidation of 9-hydroxy-5,6-dihydro-8//-pyrido[l,2-a]quinoxalin-8-one with KMn04 in H20 gave quinoxaline-2-carboxylic acid (75MI1). 

It was thought that acidic cyclization of 2-(l,2,3,4-tetrahy-droxybutyl)quinoxaline yielded 8//-pyrido[l, 2-a]quinoxalin-8-one, but later it was clarified that the product was 2-(2-pyrrolyl)quinazoline (61CH1191). 

Benzylperhydropyrido[l,2-a]pyrazin-6-one was prepared through the cyclization of 287, obtained from 285 via 286 (93JOC690). From the reaction mixture of 2,3-di(2-tetrahydrofuryl)piperazine, treated with HBr gas in AcOH at 90-95°C, then with KOH, l-(2-tetrahydrofuryl)-9-hydroxy-perhydropyrido[l,2-a]pyrazine could be isolated (61BSF2135). Cyclization of 2-(l,2,3,4-tetrahydroxylbutyl)quinoxalines in an acidic media gave 8H-pyrido[l,2-a]quinoxalin-8-ones together with a small amount of their 9-... 

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