RESUMO
The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this synthesis, a Pd-catalyzed C-H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.
Assuntos
Compostos Heterocíclicos com 3 Anéis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Catálise , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/metabolismo , Ligantes , Estrutura Molecular , Paládio/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/químicaRESUMO
The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel-Crafts acylation, Pictet-Spengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide α-bromination to functionalize a critical C-H bond, enabling a highly regioselective copper-mediated Ullmann-Goldberg-Buchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Compostos Aza/síntese química , Compostos Aza/farmacologia , Indóis/síntese química , Indóis/farmacologia , Organofosfatos/síntese química , Organofosfatos/farmacologia , Piperazinas/síntese química , Piperazinas/farmacologia , Ligação Viral/efeitos dos fármacos , Compostos Aza/química , Óxidos N-Cíclicos/química , HIV-1/efeitos dos fármacos , Halogenação , Humanos , Indóis/química , Estrutura Molecular , Organofosfatos/química , Piperazinas/química , Pró-Fármacos , Pirróis/química , EstereoisomerismoRESUMO
Here we report the solution-liquid-solid (SLS) synthesis of silicon (Si) nanowires. Nanowires are grown by trisilane (Si3H8) decomposition in a high boiling solvent, octacosane (C28H58) or squalane (C30H62), in the presence of either Au or Bi nanocrystals. To our knowledge, this is the first report of a colloidal synthetic route carried out in a solvent at atmospheric pressure that provides crystalline Si nanowires in large quantities.
RESUMO
High yields of crystalline Ge nanowires were synthesized for the first time in a conventional solvent of trioctylphosphine by disproportionating GeI2 in the presence of Bi nanoparticle growth seeds at 350 degrees C and atmospheric pressure.