Assessing a sustainable manufacturing route to lapatinib

Abstract

A synthetic route to an anti-cancer drug, lapatinib, was devised to support the development of a sustainable manufacturing process in South Africa. Quantitative metrics were employed to evaluate the sustainability...

Classic vs. C–H functionalization strategies in the synthesis of APIs: a sustainability comparison

“…In 2007, lapatinib was approved in combination with capecitabine and later, in 2013, the approval was extended to a chemotherapy-free combination with trastuzumab. Herein we cover a patented route of synthesis, 99 a cross-coupling based synthetic pathway 100 and a C–H functionalization strategy 101 toward the synthesis of lapatinib.…”

“…A very recent approach was reported by Hii and coworkers in 2022. 101 This elegant example presents a revisited route for lapatinib to define its sustainable manufacture in South Africa. As the reported synthesis was developed to work closely to solubility limits in order to favour precipitation of the obtained products, no utilization of chromatographic purification was needed through the different steps.…”

Economic kilogram-scale synthesis of the novel antiepileptic drug brivaracetam utilizing porcine pancreatic lipase

“…The designed reaction proceeded smoothly in inorganic acid, and three major products were detected by LC-HRMS analysis of the crude reaction mixture including brivaracetam acid 10, brivaracetam ester 11 and brivaracetam imine 12. In addition to the major hydrolysis pathway, the cyclization of 2 might also proceed to the direct ammoniation of the alkyl nitrile [21][22][23][24][25][26] based on the result of the detected imine 12. Of note, 20% aq.…”