2,2-DIMETHYL-3-ESTER-4-ALKOXY-6-ALKYL AMINO BENZOPYRAN DERIVATIVES AND PARALLEL SYNTHESIS OF THE DERIVATIVES ON SOLID-PHASE

摘要

PURPOSE: 2,2-Dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives and a parallel synthesis of the derivatives on solid-phase are provided. The compounds have improved lipid peroxidation inhibiting activity, and are thus useful for the prevention and treatment of disease caused by stimulation of lipid peroxidation or accumulation of oxidizing materials. CONSTITUTION: 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives are represented by the formula(5a), wherein R1 is C1-C10 saturated, unsaturated or cyclic alkyl, benzyl or substituted benzyl; R2 is C1-C10 saturated, unsaturated or cyclic alkyl, benzyl, substituted benzyl, or penethyl; and R3a is C2-C10 unsaturated or cyclic alkyl, phenyl, substituted phenyl, or 5- to 7-membered hetero ring containing a hetero atom selected from oxygen and sulfur in which the substituted benzyl or substituted phenyl is benzyl or phenyl substituted by 1 to 4 substituents selected from halogen atom, nitro, C1-C10 alkyl, C1-C10 alkoxy and C1-C10 haloalkyl. A parallel synthesis of the 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives of the formula(5) on solid-phase comprises the steps of: selectively introducing R1 substituent to nitrogen of benzopyran of a compound of the formula(1) to prepare N-alkyl substituted carbamate resin of the formula(2); adding meta-chlorobenzoic acid and alcohol into the compound of the formula(2) and reacting them to prepare 2,2-dimethyl-3-hydroxy-6-alkyl amino benzopyran resin of the formula(3); reacting 3-hydroxy of the compound of the formula(3) with electrophile selected from carbonyl halide compounds containing R3 to prepare 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran resin of the formula(4); and treating the compound of the formula(4) with trifluoroacetic acid(TFA) containing a dichloromethane solution or organic acid containing an organic solvent, wherein (P) is a polymer type solid support selected from polystyrene-divinylbenzene, methacrylic acid-dimethylacrylamide and hydroxy methacrylic acid.