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Abstract : N6-substituted adenines have received an increasing attention as inhibitors and modulators of many key biological targets and thus becoming widely used as building blocks in drug development projects. In fact, as all purines` cores, adenine derivatives suffer from a lack of regioselectivity which makes their regioselective synthesis a difficult mission. However, since the synthesis of 2-chloro-N-(9H-purin-6-yl) acetamide has not been reported before in spite of its role as a possible starting material for many drug candidates, this paper aims to study the effect of experimental parameters on the synthesis process and product purity of this compound. The monitoring was carried out by liquid chromatography with tandem mass spectrometry (LC-MS/MS) via total ion scan in addition to Single Ion Monitoring (SIM) which searches for a specific single ion mass in the chromatogram. The synthesis depends on the acylation of adenine with 2- chloro acetyl chloride. Three different conditions were applied. First, in a biphasic system (aniline acylation method). Second, in a dry solvent. Third, in acetate buffer solution (lidocaine synthesis method). As a result, lidocaine synthesis method did not succeed, while the detailed analysis of LC/MS/MS chromatograms indicates that the diamide 2-chloro-N-(9-(2-chloroacetyl)-9H-purin-6-yl) acetamide is detected as a possible byproduct impurity in the reaction product of the two other methods. In addition, both of adenine and 2- chloroacetylchloride were found as starting materials impurities.