Route Optimization and Synthesis of Taxadienone
25 Jun 2024 | Contributor(s):: Krasutsky, Sergiy G., Jacobo, Sheila H., Tweedie, Scott R., Krishnamoorthy, Ravi, Filatov, Alexander S.
Early process development toward the scalable production of taxadienone on a decagram scale is described. A continuous flow reactor was employed to safely run a potentially hazardous cyclopropane ring opening. The route featured two copper-mediated additions, a Diels–Alder reaction and a...
Synthesis of a Highly Functionalized Quinazoline Organozinc toward KRAS G12C Inhibitor Divarasib (GDC-6036), Enabled through Continuous Flow Chemistry
25 Jun 2024 | Contributor(s):: Kelly, Sean M., Lebl, René, Malig, Thomas C., Bass, Thomas M., Kummli, Dominique, Kaldre, Dainis, Orcel, Ugo, Tröndlin, Lars, Linder, David, Sedelmeier, Joerg, Bachmann, Stephan, Han, Chong, Zhang, Haiming, Gosselin, Francis
The development of a scalable continuous flow process to synthesize a densely functionalized quinazoline organozinc intermediate toward KRAS G12C inhibitor divarasib (GDC-6036) is reported herein. A traditional cryogenic batch metalation process was initially employed, but instability of the...