Synthesis Of 3-amino-5-(4-methoxyphenyl)Pyrazol

The research of heterocyclic compound has been one of the hot spots in the modern medicine research process. In recently years, about 90 % of drug patents have been declared all over the world belong to heterocyclic compound. Nitric compound is the most important of the heterocyclic compound in the research domain. Simultaneously the pace of development research about pyrazol compound is much more rapid than others. The kinds of pyrazol compound are great quantity because there are 1,3,4,5 - four locations in pyrazol compound can be substituted by other groups, this characteristic also makes lots of pyrazol compounds and their substitutions which with biology active. Pyrazol compounds both contain amido group and phenyl group are provided with pharmacology active about treat disease of cardiovascular and prevent hypertension and so on. However I can't find any document about synthesis of 3-amino-5-(4-methoxyphenyl)pyrazol through search a large number of literatures. Certainly the synthetic route is immature and the experiment is provided with exploratory.3-amino-5-(4-methoxyphenyl)pyrazol was synthesized from 4-methoxybenzoic acid methyl ester via two reactions, the overall yield was up to 46.07 %. The first step 4'-methoxybenzoylacetonitrile was synthesized and the second step 3-amino-5-(4-methoxyphenyl)pyrazol was synthesized. Reaction conditions about solvent, volume of material, volume of solvent, reaction temperature and reaction time were observed through Orthogonal experimental design. From these experiments, some conclusions can be educed. The optimum conditions with 4'-methoxybenzoylacetonitrile are as follows, 4-methoxybenzoic acid methyl ester 16.62 g, sodium hydride 6 g, acetonitrile 10.47 mL, the volume of toluene is 80 mL, the reaction temperature is 90℃and the reaction time is 20 h. The product is yellow needle-like crystals, melting point 129.4-130.3℃and the overall yield is 74.11 %. The optimum conditions with 3-amino-5-(4-methoxyphenyl)pyrazol are as follows, 4'-methoxybenzoylacetonitrile 17.5 g, hydrazine hydrate 5.00 g, the volume of grain alcohol is 90 mL, the reaction temperature is 80℃(refluxing) and the reaction time is 6 h. The product is white solid powder, melting point 143.7-145.2℃and the overall yield is 62.17 %. The structures of products are confirmed by IR,HPLC-MS,1H NMR and elemental analysis.