4- Phenyl-4- ethyl perhydro

The parent system (99) has been obtained by lithium aluminum hydride reduction of perhydro-imidazo[l,5-a]pyridine-l,3-dione (from ethyl 2-piperidine carboxylate and cyanic acid) and by ring closure of 2-aminomethylpiperidine with formaldehyde. 3-Substituted derivatives have also been described. The 3-phenyl- and 3-/-butyl derivatives (but not the propyl and benzyl derivatives) show ring-chain tautomerism (70JHC355). 

The 3-imino group of 4-cyano-2-ethyl-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione was acylated with phenyl isocyanate (78MI1). The imino group of l-imino-4-cyano-3-methylthio-l//-pyrido[l,2-cjpyrimidine was alkylated and acylated with methyl iodide and acetic anhydride (75YZ13). Reaction of 3-amino-4-phenyl-4-[2-(A, N-di-n-pro-pylamino)ethyl-4,4 a,5,6,7,8-hexahydro-l //-pyrido[l, 2-c ]pyri midin-l-one with acetic anhydride in pyridine and with sodium nitrite in aqueous acetic acid afforded 3-acetamido and perhydro-l,3-dioxo derivatives, respectively (87USP4680295). 

The enantiomerically pure perhydro-l,3-oxazine-2,6-dione (72 R = menthyl Ar = 4-methoxyl-phenyl) reacts with benzaldehyde to give the benzylidene derivative (73). This compound shows high diastereofacial selectivity ( 98%) when used as either an oxadiene, or as a Michael acceptor. For example, with 2-methoxypropene, followed by thermolysis of the adduct in boiling 1,4-dioxane, it affords the ketoaldehyde (74) and with ethyl magnesium bromide it gives the adduct (75), acidic hydrolysis of which yields the chiral acid (76) (Scheme 15) <92CL485,92CPB1972). 

Another amine surrogate is perhydro 1,3,5-triazine 4.40, which reacted with 4.37 to give methyl 2,2-dimethyl-N-benzyl-3-aminopropanoate (4.41). The analogous N-isopropyl, N-ethyl, and N-phenyl derivatives were also prepared, as were the 2-methyl propanoate derivatives.21... 

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