PREPARING METHOD OF CHROMONE-3-CARBOXYL ACID DERIVATIVES USING PARALLEL COMBINATORIAL CHEMISTRY IN SOLUTION PHASE

摘要

A preparing method of chromone-3-carboxyl acid derivatives is provided to improve preparation yield and reduce the preparation time by preparing various derivatives in each step through a series of reactions without purification by using parallel combinatorial chemistry in solution phase. A preparing method of chromone-3-carboxyl acid derivatives represented by the formula(1) comprises the steps of: o-acetylsalicylic acid chloride represented by the formula(2) with tertiary butoxycarbonylmethylene triphenylphosphorane represented by the formula(7) in the presence of catalyst to prepare phosphorane compound represented by the formula(3); deacetylating the phosphorane compound represented by the formula(3) in the presence of base to prepare compounds represented by the formula(4); reacting the compounds represented by the formula(4) with an excessive amount of acid chloride in the presence of base and catalyst to prepare compounds represented by the formula(5); preparing compounds represented by the formula(6) from the compounds represented by the formula(5) through Wittig reaction; and deesterifying the compounds represented by the formula(6) under acid condition to remove tertiary butyl group, wherein R1 is hydrogen, chlorine, bromine, methoxy group or methyl group, and R2 is aromatic group or hetero aromatic group substituted by chloride, fluorine, methoxy group, methyl group or hydroxy group.