There are catalysis geniuses (looking at you, process chemists!) and then there are those of us just looking to put compounds in vials. Here are the simplest conditions that’ll get you what you want 90% of the time. Beyond that you’ll need to ask a guru like Nick White or Malcolm Huestis. Hope this helps. …
Scientists from GlaxoSmithKline’s Stevenage site have an excellent article in J. Med. Chem. showing that cyclopropyl pyran (CPP) groups can serve as viable isosteres to N-pyrimidyl morpholines thanks in part to favorable cyclopropane σ -> aryl π interactions. N-aryl morpholines are privileged motifs in drug discovery, and suitable hydrogen-bond accepting isosteres are scarce. This is …
BMS-986142 is a reversible BTK inhibitor with two axial stereocenters. BMS synthetic chemists were able to make >200 kilos of this compound as a single isomer using this route. Wow. Atropisomers are a nightmare in drug discovery. Axial stereocenters are not easy to set predictably, separation of isomers is a pain, and the products are …
Adventures in Atropisomerism: A Case Study from BMS Read More »
Knochel’s group has shown that you can fluorinate Grignard reagents without decomposition via single-electron transfer reactivity (SET) by a simple solvent switch from THF to DCM. A common way to prepare aryl fluorides is through lithium-halogen exchange, followed by trapping with N-fluorosulfonimide (NFSI). This isn’t always viable, as the alkyllithium reagents used in the exchange …