Potential antimitotic agents. Synthesis of some ethyl benzopyrazin-7-ylcarbamates, ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates, and ethyl pyrido[3,4-e]-as-triazin-7-ylcarbamates

Ring analogues and derivatives of the 1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 29), antimitotic agents with antitumor activity, were prepared in the search for compounds with greater selectivity. Methods were developed for the conversion of substituted benzoic acids (1-4) to give benzopyrazines (12-16 and 21) and of substituted pyridin-2-carbamates (23, 38, and 41) to give 2-aminopyrido[3,4-b]pyrazin-7-ylcarbamates (32 and 36) and pyrido[3,4-e]-as-triazin-7-ylcarbamates (47 and 50). In vitro evaluation indicated that activity was reduced by removal of the pyridine ring nitrogen of 29 to give 14 and was destroyed by increasing the basicity of the pyrazine ring of 29 to give 32 and 47.