Synthesis of 3-Hydroxy-6-oxo[1,2,4]triazin-1-yl Alaninamides, a New Class of Cyclic Dipeptidyl Ureas

Cyclohexyl or benzyl isocyanide, benzoyl-, or 4-methoxybenzoylformic acid and semicarbazones
underwent Ugi reactions in methanol for 3 days to give the Ugi adducts, which were then stirred with
sodium ethoxide in ethanol for 12 h to give 3-hydroxy-6-oxo[1,2,4]triazin-1-yl alaninamides. The X-ray
diffraction structure of the first example showed the tautomer having the proton in the O2 atom that was
fixed in the crystal by packing in dimers with a H-bond distance of 1.9 Å. Selected [1,2,4]triazines were
treated with diazomethane for 12 h to get the O-methyl derivatives. Both hydroxy and O-methyl derivatives
obtained by this method constitute a new class of pseudopeptidic [1,2,4]triazines composed of two different
amino acids, arylglycine and alanine derivatives, in which the N-terminal arylglycine and the peptidic
amide nitrogen atoms are bonded through a urea moiety.

环己基异氰或苄基异氰、苯甲酰基（benzoyl-）或4-甲氧基苯甲酰甲酸与缩氨基脲（semicarbazones）在甲醇中进行乌吉反应（Ugi）3天，得到乌吉加合物（Ugi adducts）；随后将该加合物与乙醇钠在乙醇中搅拌12小时，得到3-羟基-6-氧代[1,2,4]三嗪-1-基丙氨酰胺类化合物。首个实例的X射线衍射（X-ray diffraction）结构显示，该互变异构体的质子位于O2原子，在晶体中通过二聚体堆积固定，其氢键键长为1.9 Å。选取部分[1,2,4]三嗪类化合物与重氮甲烷反应12小时，制得对应的O-甲基衍生物。通过该方法获得的羟基衍生物与O-甲基衍生物，均属于一类新型类肽[1,2,4]三嗪（pseudopeptidic [1,2,4]triazines）；该类化合物由芳基甘氨酸（arylglycine）与丙氨酸衍生物两种不同氨基酸构成，其中N端芳基甘氨酸与肽酰胺氮原子通过脲基（urea moiety）相连。