Parallel synthesis of 1,3-dihydro-1,4-benzodiazepine-2-ones employing catch and release.
An efficient solid-phase method has been developed for the parallel synthesis of 1,3-dihydro-1,4-benzodiazepine-2-one derivatives. A key step in this procedure involves catching crude 2-aminobenzoimine products 4 on an amino acid Wang resin 10. Mild acidic conditions then promote a ring closure and in the same step cleavage from the resin to give pure benzodiazepine products 12. The 2-aminobenzoimines 4 can be synthesized from either 2-aminobenzonitriles 1 and Grignard reagents 2 or from iodoanilines 5 and nitriles 7 allowing a range of diversification. Further diversification can be introduced to the benzodiazepine products by N-alkylation promoted by a resin bound base and alkylating agents 13.
Laustsen
Line S
LS
Medicinal Chemistry Research I, Chemical Research, Leo Pharma, Ballerup 2750, Denmark.
Sams
Christian K
CK
D010129:4-Aminobenzoic Acid / Q000737:chemistry; D000478:Alkylation; D000814:Aniline Compounds / Q000737:chemistry; D001569:Benzodiazepines / Q000138:chemical synthesis; D001570:Benzodiazepinones / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D007097:Imines / Q000138:chemical synthesis; D013058:Mass Spectrometry; D008956:Models, Chemical; D009570:Nitriles / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry
D000814:Aniline Compounds; D001570:Benzodiazepinones; D007097:Imines; D009570:Nitriles; D012117:Resins, Synthetic; D001569:Benzodiazepines; C023650:aniline; D010129:4-Aminobenzoic Acid