Abstract
An efficient solid phase regioselective alkylation at the N4 position of a 3-oxo-1,4-benzodiazepine template exemplified by 4-H-2,3,4,5-tetrahydro-7-iodo-3-oxo-1H-1,4-benzodiazepine-2-acetate-polymer ester is described. Further chemical elaboration at position 7, utilizing a modified Heck reaction, allows the incorporation of amides from primary or secondary amines. The two diversity points at positions 4 and 7 were utilized to synthesize a 28-membered, combinatorial array on Sasrin resin in moderate yields and > 80% purity. Having validated the chemistry on solid support, a combine and split approach to prepare a bead-bound combinatorial library is achievable utilizing similar experimental practices and procedures as in the array synthesis.