# Academic–Industrial Collaboration in Synthesis with Real-Time Impact in Medicinal Chemistry: Discovery of Cystic Fibrosis C2 Corrector ABBV-602

## TL;DR

A collaboration between academia and industry led to the development of a new drug for cystic fibrosis by improving chemical synthesis methods.

## Contribution

A novel catalyst-additive system was developed for efficient cyclopropanation, enabling the discovery of CFTR corrector ABBV-602.

## Key findings

- A joint team developed a unique catalyst-additive system for cyclopropanation with broad pharmaceutical relevance.
- The optimized method accelerated the discovery of the CFTR corrector ABBV-602.
- A flow procedure enabled kilogram-scale production of the carbene precursor.

## Abstract

This article highlights synergistic real-time interactions
between
academic and industrial groups that drove innovations in both medicinal
chemistry and catalysis. An AbbVie medicinal chemistry team had identified
a promising series of trisubstituted cyclopropanes during a drug discovery
campaign focused on developing CFTR C2 correctors for the treatment
of cystic fibrosis. However, this unique chemical space was challenging
to efficiently explore due to known limitations with previously established
cyclopropanation reaction conditions. By expanding upon an existing
precompetitive relationship with the Davies group at Emory University
who are pioneers in development of methods for highly diastereo- and
enantioselective cyclopropanations, a joint industry-academia team
collaborated to discover a unique catalyst-additive system for this
challenging transformation that had a broad and pharmaceutically relevant
substrate scope. The optimized method was immediately applied to accelerate
medicinal chemistry progress in the series, leading to the identification
of novel CFTR corrector ABBV-602. Finally, a flow procedure was developed
for generating the carbene precursor which enabled the reaction to
be carried out on kilogram scale.