15° SEMINARIO QUÍMICA ORGÁNICA IQUIR 2023

SEMINARIO QUÍMICA ORGÁNICA 04-09-23

EXPOSITOR: Qco. Msc. Javier Cala

TÍTULO: "Descubrimiento y síntesis de Entrectinib, nuevo anticancerígeno 3-aminoindazol"

FUENTE: 

1) Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor

Maria Menichincheri et al. J. Med. Chem. 2016, 59, 7, 3392–3408
https://doi.org/10.1021/acs.jmedchem.6b00064

2) Total Synthesis of Entrectinib with Key Photo-Redox Mediated Cross-Coupling in Flow
Morgan J. Cordell, Matt R. Adams, Dr. Jean-François Vincent-Rocan, Dr. John G. Riley
Eur. J. Org. Chem. 2022, e202101143
https://doi.org/10.1002/ejoc.202101143

DÍA, HORA y LUGAR: Lunes 4 de septiembre de 2023, 14:00 h, Aula 18 y virtual.

Modalidad virtual, Link: meet.google.com/hjn-ygro-twf (Plataforma MEET GOOGLE)

Resumen: By using photo-redox catalysis in flow the newly marketed drug entrectinib (referred to by the brand name Rozlytrek) was synthesized in 6 linear steps from readily available building blocks under mild conditions. Evaluation of multiple intermediates for their use in the critical C−N amination step in flow led to the finding that more electron deficient aryl-halides achieve higher conversion to the desired product. Data supports that more electron rich aryl-halides undergo a significant amount of hydro-dehalogenation compared to the productive C−N bond formation. Through evaluating various entry points into the synthesis of entrectinib, shorter routes were identified albeit in low yields. The modularity of this route will allow chemists to rapidly synthesize a diverse library of compounds through this route. Via different synthetic intermediates, a scale-up route was discovered for the synthesis of entrectinib using photo-redox in flow in less steps than previously reported, highlighting the utility of flow chemistry in the pharmaceutical industry.