Hexahydro-8//-pyrido pyrazines

Structure of 4//-pyrido[l,2-a]pyrazines 348-350 was confirmed by X-ray investigations (99JPR332). The stereostructure of 1,3,4,6,1 l,lla-hexahydro-2/f-pyrazino[l,2-A]isoquinoline-l,4-dione 351 was determined by X-ray investigation (01TL543). 

Racemic or optically active perhydropyrido[l,2-a]pyrazines were obtained by reduction of 9a5-perhydropyrido[l,2-u]pyrazin-4-one with LAH in Et20 at room temperature (99H(51)2065) and by reduction of perhydropyr-ido[l,2-u]pyrazine-l,4-diones with LAH in boiling THF (97USP5703072, 00JAP(K)00/86659). Treatment of (9uS)-2-(fcrf-butoxycarbonyl)perhydro-pyrido[l,2-u]pyrazin-4-one with LAH in Lt20 afforded (9uS)-2-fcrf-butox-ycarbonyl-l,6,7,8,9,9a-hexahydro-2//-pyrido[l,2-a]pyrazine (99H(51)2065). 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

Structures of 3-[(4-methylphenyl)amino]-47/-pyrido[l,2-tf]pyrazine-4-thione, iV-tosyl-3-[(4-methylphenyl)a-mino]-4//-pyrido[l,2-tf]pyrazine 4-imine, and 246 were confirmed by X-ray investigations <1999JPR332>. The stereostructures of (4A,llaA)-lla-ethoxycarbonylT,3,4,6,lla-hexahydro-l,3,4,6,ll,lla-hexahydro-4-methox-ycarbonyl-l-oxo-[l,4]oxazino[4,3-A isoquinoline <1995ZK787>, 2//-pyrazino[l,2- ]isoquinolinc-l,4-dione 247 <2001TL543>, 4-benzyl-2-methyl-1,3,4,6,7,11 b-hcxahydro-2//-pyrazino[2,l -zz] isoqu incline-3,6-dione... 

Reduction of 2-benzyl-2,3,4,6,7,8-hexahydro-l//-pyrido[l,2-a]pyrazin-l-one (73CPB1248) and l-oxo-l,2,3,4-tetrahydropyrazino[l,2-b]isoquinolinium bromide (73CPB2039) with NaBH4 yielded perhydropyrido[l,2-fl] pyrazin-1-one and l,3,4,6-tetrahydro-2//-pyrazino[l,2-6]isoquinolin-l- one, respectively. 

Reaction of l-(3,4-dimethoxybenzyl)-9-hydroxy-l,2,3,4-tetrahydro-8//-pyrido[l,2-a]pyrazin-8-one with 37% formaldehyde solution gave a tetracyclic tetrahydroprotoberberine analogue in a Mannich-type reaction (78AJC187). Reactions of 2,3,4,4a,5,6-hexahydro-l//-pyrazino[l,2-a]-quinolines with 1 W-pyrrolo[2,3-h]pyridine in the presence of 37% aqueous CH20 and AcONa in AcOH, and with 3-dimethylaminomethyl-l //-pyrrolo[2,3-h]pyridine afforded 3-[(l//-pyrrolo[2,3-h]pyridin-3-yl)methyl] derivatives (94MIP6 96USP5576319). 

Hexahydro-l//-pyrido[l,2-a]pyrazin-l-ones were prepared by oxidation of 2-substituted perhydropyrido[l,2-a]pyrazines and perhydro-pyrido[l,2-a]pyrazin-l-one with Hg(OAc)2 in 5% aqueous AcOH (73CPB1248). Oxidation of l,3,4,6,ll,lla-hexahydro-2//-pyrazino[l,2-bjisoquinoline with Hg(OAc)2 in 5% aqueous AcOH gave the 6-oxo derivative [73CPB2039 77IJC(B)70]. l,3,4,6,ll,lla-Hexahydro-2//-... 

---