2- Substituted-7- perhydropyrido pyrazine

Methyl 2-substituted perhydropyrido[l,2-u]pyrazine-8-acetates were obtained by catalytic hydrogenation of 2-substituted 8-(methoxycarbonyl-methylene)perhydropyrido[l,2-a]pyrazines over 10% Pd/C catalysts (00JAP(K)00/86659). A side chain 4-pyridyl group was hydrogenated over Pt02 catalysts to yield a 4-piperidyl derivative. 

Substituted perhydropyrido[l,2-n]pyrazines were reacted with 2-fluorobenzohydroximinoyl chlorides in the presence of DBU in CHCI3 to yield a isomeric mixture of 7-substituted 2-[(hydroxyimino)phenylmethyl]-perhydropyrido[l, 2-u]pyrazines (99MIP9). 

Substituted perhydropyrido[l,2-a]pyrazine-l,4-diones were obtained when methyl A-[2-(benzyloxycarbonylamino)acetyl]-4-substituted pipecoli-nates were hydrogenated over 10% Pd/C catalyst in MeOH, and then the methanolic solutions were refluxed (00JAP(K)00/86659). 

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//-... 

Heating alkyl 6-substituted l-[2-(p-nitrophenylcarbonylamino)ethyl]-pipecolinates in boiling 6N HC1 afforded 6-substituted perhydropyrido[l,2-a]pyrazin-l-ones (66JMC311,68USP3388128). 

Thionyl chloride has been used to convert the alcohol 56 into the cyclized quaternary salt 57. Reduction of the nitrile 58 with Raney nickel and hydrogen gave the 1-oxo compound 60 (R = H), ° presumably by way of the intermediate 59. This intermediate is also involved in the preparation of compound 60 (R = H) by treatment of the ester 61 with ethyleneimine. The optically active ester 61 has been converted by this route into perhydropyrido[l,2-a]pyrazines of known configuration. When this reaction was repeated with the methyl-substituted piperidine... 

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