title: A new strategy for the construction of the imidazo[1,5-a]quinoxalin-4-one ring system and its application to the efficient synthesis of BMS-238497, a novel and potent Lck inhibitor.
abstract: A new efficient strategy was developed for the construction of the imidazo[1,5-a]quinoxalin-4-one ring system. The new method involves condensation of o-nitroaniline with glyoxylate in methanol followed by treatment of the resulting alpha-(o-nitroanilino)-alpha-methoxy acetate with tosylmethyl isocyanide (TosMIC) reagent to give 1-(o-nitrophenyl)imidazole-5-carboxylate. Reductive cyclization of the nitro imidazole carboxylate afforded imidazo[1,5-a]quinoxalin-4-one in three steps and 60% overall yield. The new method was successfully applied to the synthesis of BMS-238497, a novel and potent Lck inhibitor.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA. bangchi.chen@bms.com
authors.forename: Bang-Chi
authors.initials: BC
authors.lastname: Chen
authors.forename: Rulin
authors.initials: R
authors.lastname: Zhao
authors.forename: Mark S
authors.initials: MS
authors.lastname: Bednarz
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Sundeen
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006038:Glyoxylates / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C485021:4-(2-chloro-6-methylphenylamino)-7,8-dimethoxyimidazo(1,5-a)quinoxalin-4-one; D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D006038:Glyoxylates; D007093:Imidazoles; D011810:Quinoxalines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)