Preparation Of A Fully Substituted Purine Library And Synthesis Of Novel Pyrimido-[4,5-b][1,4]Benzodiazepines

Purine and Benzodiazepine analogues are considered of privileged structures in medicinal chemistry and often shown to possess a wide range of interesting pharmacological activities. In this thesis, a 135-member library of tetra-substituted purines was generated in solution phase from readily available amidines, amines, carboxylic acids or its derivatives in good to high yields and high purity, and a methodology for the preparation of novel 4-chloro-pyrimido[4,5-b][1,4]benzodiazepines was developed. In the first part, a library of tetra-substituted purine analogues was readily prepared via parallel synthesis. This strategy relied on a key cyclization of a 4,5-diaminopyrimidine with either a carboxylic acid or its derivative to construct the 2,8,9-trisubstituted 6-chloropurine core. Further elaborations of this core allowed the introduction of other diversity points. This methodology was demonstrated through the preparation of a 135-membered library of tetra-substituted purines in good yields and high purity. In the second part, a methodology was developed for the efficient synthesis of novel 4-chloro-pyrimido[4,5-b][1,4]-benzodiazepines. The key is the intramolecular Friedel-Crafts cyclization of 5-amino-4-(N-substituted)anilino-6-chloropyrimidine with either a carboxylic acid or its derivatives to construct the 4-chloro-pyrimido[4,5-b][1,4]benzodiazepine core. Subsequent nucleophilic substitution allows the introduction of one more diversity point in the target molecules.