Synthesis Of 2, 6-Bis(3-methyl-1-Hpyrazol-1-yl)-4-aminopyridine

A new bifunctional chelate intermediate of time-resolved flurescence immunoassay,2,6 -bis(3-methyl-1H-pyrazol-1-y1)-4-aminopyridine was prepared from 2,6-dichloropyridine by oxidation,nitration,reduction and nucleophilic substitution reaction.The effect on oxidation, nitration,reduction and nucleophilic substitution reaction were studied based on reaction mechanism. Response to various factors,and unit reaction was optimized to obtain the optimal conditions.Optimal conditions of oxidation were obtained as follows:the molar ratio of 2,6-dichlor-opyridine to hydrogen peroxide was 6:11,trifluoroacetic acid 35mL,reaction 3h under 100℃, the yield was 84.15%.Optimal conditions of nitration were obtainedas follows: 2,6-dichloropyridine-1-oxide 1.28g,Potassium nitrate 7.45g,reation 1h under 75℃,the yield was 93.26%.optimal conditions of reduction were obtained as follows: 2,6-dichloropyridine-4-nitropyridine-1-oxide 1.21g,ice acid 35mL,iron powder 2.32g, reaction 2h under 100℃.the yield was 84.04%.optimal conditions of nucleophilic substitution reaction were obtained as follows:the molar of 4-amino-2,6-dichloropyridine to 3-methyl-pyrazole topotassium was 1:4:4,diglyme 36mL,reaction 100h under 163℃,the yield was 28.55%.The total yield was 18%.The product was characterized bymelting point, IR,~1H NMR,LCMS and element analysis.