title: Regioselective alkylation at the N4 position of a 3-oxo-1,4-benzodiazepine on solid support.
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.
authors.affiliation: Department of Medicinal Chemistry, Research and Development Division, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA 19406-0939, USA. fadia_e_ali@sbphrd.com
authors.forename: F E
authors.initials: FE
authors.lastname: Ali
authors.forename: C C
authors.initials: CC
authors.lastname: Yuan
authors.forename: S T
authors.initials: ST
authors.lastname: Ross
authors.forename: L B
authors.initials: LB
authors.lastname: Hall
mesh_terms: D000478:Alkylation; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
chemical_list: D001570:Benzodiazepinones