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.
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.
Chen
Bang-Chi
BC
Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA. bangchi.chen@bms.com
Zhao
Rulin
R
Bednarz
Mark S
MS
Wang
Bei
B
Sundeen
Joseph E
JE
Barrish
Joel C
JC
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
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)