Synthesis Of3(5)-alkly-4-amino-pyrazole Compounds

At present, heterocyclic compounds and heterocyclic chemistry have broad prospects and play a decisive role in the research and development of biological medicine and new pesticide production.3(5)-alkyl-pyrazole-4-amine compounds belongs to heterocyclic compounds which could be used for intermediates or building blocks for medicinal chemistry. Most of the research findings of these compounds are focused on aryl-substitution derivatives. The relative3-positon or5-position alkyl-substitution pyrazole derivatives is still a blank field for heterocyclic synthesis. Four new compounds of3(5)-alkyl-4-amino-pyrazole were successfully synthesized by two different synthetic routes:3(5)-cyclopropyl-1-NBoc-piperidineyl-pyrazol-4-amine (Target compound A and Target compound B),3(5)-cyclopropyl-l-pyranyl-pyrazol-4-amine (Target compound C and Target compound D). All the compounds could be used as building blocks or intermediates for medicinal chemistry and the final targets were characterized by LC-MS,’H-NMR,13C-NMR, NOSEY spectrums.1. a,B-Unsaturated carbonyl compound was synthesized from cyclopropyl ethanone by3steps and prepared1H-pyrazole scaffold by hydrazine cyclization reaction. The scaffold was reacted with tosylate intermediates to make3-postion substituted pyrazole derivatives with high regio-selectivity. After deprotection reaction and purification by recrystallization under low temperature, pure final target compound A and B were prepared.2. Target compound C and D were synthesized by the cyclization reaction from hydrazine derivatives and a,B-unsaturated carbonyl intermediates with high regio-selectivity. Key intermediate hydrazine derivatives were prepared from ketone starting materials.3. Around100grams of final target compounds A and B which contain no regio-isomer were scaled up in laboratory by process optimization. The synthetic routes were proved to be highly repeatability.4. Two synthetic routes were proved to be used for other3(5)-position substituted pyrazole derivatives, such as ethyl, iso-propyl, trifluromethyl, difluromethyl, methyl ester besides cyclopropyl-substitued compounds, which could be a reference for scientific study of synthesis multi-substituted pyrazole compounds.