MCC/SNAr methodology.: Part 2:: Novel three-step solution phase access to libraries of benzodiazepines

New developments in the search for novel pharmacological agents over the last decade have focused on the preparation of chemical libraries as sources for new leads for drug discovery. To aid this search a plethora of personal synthesizers and new automation technologies have emerged to help fuel the lead discovery engines of drug discovery organizations. In fact, multi-step solid-phase syntheses of diverse libraries in excess of 10,000 products are now feasible via split and mix techniques. At the same time, a multitude of more efficient, diversity or target oriented solution phase chemical methodologies have appeared in the chemical literature, which have enabled the relatively facile construction of successful lead generation libraries with low FTE input and little capital expenditure. This communication reveals a further application of N-BOC-alpha-aminoaldehydes in the Ugi condensation reaction, followed by a secondary SNAr cyclization, accessing arrays of biologically relevant benzodiazepines in good yield and overall purity. (C) 2003 Elsevier Science Ltd. All rights reserved.