ER-38930

Chemical Name: 4-[5-(1,5-Diisopropylpyrazol-3-yl)-1H-pyrrol-2-yl]benzoic acid
CAS No. 187402-44-4
项目整合开发状态: Biological Testing
项目研究机构: Eisai (Originator)
合成路线:Condensation of 3-methyl-2-butanone (I) with methyl 2-methoxyacetate (II) by means of sodium in toluene gave diketone (III).Pyrazole (IV) was prepared by treatment of diketone (III) with hydrazine.Subsequent alkylation of pyrazole (IV) with isopropyl iodide in the presence of sodium hydride provided a mixture of N-alkylated regioisomers (V) and (VI).The desired minor isomer (V) was demethylated with BBr3 and the resulting alcohol (VII) was oxidized to aldehyde (VIII) using manganese dioxide.Addition of vinylmagnesium bromide to the formyl group of (VIII) produced allylic alcohol (IX),which was further oxidized to ketone (X) with MnO2.The benzoin-type condensation of unsaturated ketone (X) with aldehyde (XI) in the presence of 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride furnished the 1,4-diketone (XII).Cyclization of (XII) to pyrrole (XIII) was carried out by treatment with ammonium acetate in refluxing MeOH.Finally,ester hydrolysis by means of NaOH gave rise to the corresponding carboxylic acid.