Pyrazino pyrimidine-3-carboxylates

Most syntheses of this type have followed the classical Gould-Jacobs pattern (Section 2.15.5.4.2) in which 2-aminopyrazines bearing a 6-substituent give esters of 8-oxopyrido[2,3-f ]pyrazine-7-carboxylic acids (424) via the usual intermediate ethoxy-methylenemalonate adducts. In some cases the isomeric pyrazino[l,2-a]pyrimidines are formed in addition (e.g. 74CPB1864). 

The saturated pyrazino[l,2- ]pyrimidin-9-one 129 was obtained by a tandem cyclization from the ct-keto carboxylic acid 128 and /V-(2-aminocthyl)-l,3-propancdiaminc (Equation 15) <1997ACS742>. 

Pyrazino[l,2-z]pyrimidine-6,8-dionc was prepared from [3+3] atom fragments by reacting 6-hydroxypyrimidine-4-carboxylic acid with 2-aminoacetaldehyde dimethyl acetal <2005W02005/016927>. 

Vovk MV, Mel nichenko NV, Tsymbal IF, Kushnir OV (2011) Synthesis of alkyl hexahydro-pyrazino-[l,2-c]pyrimidine-9-carboxylates. Chem Heterocycl Comp 47 989-995... 

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