Libraries of N-alkylaminoheterocycles from nucleophilic aromatic substitution with purification by solid supported liquid extraction

Heterocycles containing 2 or 3 chlorine atoms have been converted to libraries of N-alkylaminoheterocycles by parallel solution phase nucleophilic aromatic substitution. The first chloride displacement was achieved with stoichiometric nucleophilic alcohols, or amines. In the final substitution, excess amine was used to ensure that all active electrophiles were consumed. The excess amine and salts were removed by automated solid supported liquid extraction (SLE). SLE is partition chromatography using buffered water immobilized on a solid support and elution by a water immiscible solvent. This is a high throughput method for liquid-liquid extraction which is easily automated using simple liquid handling robotics. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.