Impurity profile study of zaleplon

Abstract Zaleplon is a pyrazolopyrimidine derivative and possesses sedative and hypnotic properties. Seven unknown impurities in zaleplon bulk drug at levels below 0.1% were detected by reverse-phase high performance liquid chromatography (HPLC). The starting material, 3-amino-4-cyanopyrazole and an intermediate, N -[3-[3-(dimethylamino)-1-oxo-2-propenyl]-phenyl]- N -ethylacetamide (DOPEA) were also present in the sample at a level below 0.1%. The molecular weights of impurities were determined by LC-MS analysis. These impurities were isolated from crude samples of zaleplon using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, N -(3-(3-(4-amino-2H-pyrazolo [3,4-d]pyrimidin-6-yl) pyrazolo[1,5-a] pyrimidin-7-yl)phenyl)- N -ethylacetamide (impurity I); N -[3-(3-carboxamidopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]- N -ethylacetamide (impurity II); N -[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide (impurity III); N -[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]- N -methylacetamide (impurity IV); N -[3-(3-cyanopyrazolo[1,5-a] pyrimidin-5-yl)phenyl]- N -ethylacetamide (impurity V); N -[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl]- N -ethylamine (impurity VI); N -[3-(3-cyano-6-[(E)-3-(( N -ethyl- N -acetyl)amino)phenyl-3-oxoprop-1-enyl] pyrazolo[1,5-a]pyrimidin-7-yl) phenyl]- N -ethylacetamide (impurity VII). Structural elucidation of all impurities by spectral data ( 1 H NMR, 13 C NMR, MS and IR) and formation of these impurities are discussed in detail.