The Lab Notes

Process chemists at Genentech recently published their work on development of a kilo-scale synthesis of JAK-1 inhibitor- GDC-4379 (Figure 1).1The central heterocyclic core of the molecule consists of a 4-aminopyrazole moiety (elaborated as the pyrazolopyrimidene amide- presumably the inhibitor hinge binding fragment in the kinase active site) with an additional aryl substituent at C-3 and…

Oxidation of allylic alcohols to enones, although on paper a simple reaction, usually requires insidiously toxic metals or metalloids such as chromium and selenium or hazardous peroxy- reagents.1 Scale-up of these methods remains particularly challenging. A team from GSK found themselves in precisely this position when developing a synthetic route to a steroid-derived HIV maturation…

The importance of methylation in the discovery and development of bio-active small molecules is well known. I presented a webinar a couple of years ago on the “The magic methyl in medicinal chemistry,” demonstrating the unique properties of this, the simplest functional group.1 I also reviewed the state of the art in synthetic approaches to…

Perhaps the best-known ring-expansion reaction is the Baeyer-Villiger oxidation, first reported in 1899- not surprisingly by Adolf von Bayer and Victor Villiger. As we’re all aware, reaction of a carbonyl with a peracid generates a Criegee-type intermediate that undergoes rate-limiting concerted rearrangement to form an ester or lactone. The migration order is substituent dependant, with…

The first electrophilc aromatic substitution reaction you were taught as an undergraduate was almost certainly nitration.1 Nitration and subsequent reduction of the aryl nitro group to an aniline via high temperature metal catalysed hydrogenation remains an important industrial process. The reduction has many flavours- both in terms of the substitution pattern on the aryl (and…

The ability to handle gaseous reagents presents a number of challenges for synthetic chemists. The problem becomes particularly acute when scaling up biphasic (liquid/gas) or even triphasic (gas/liquid/solid) systems due to limiting mass transfer effects. Pressure vessels or autoclaves are also not always practical and easy to come by. A practical solution to this (if…

To celebrate International Women's Day 2022  - Helen Spencer (Consultant BDM and Marketer) asked Scientific Update Ltd joint owners and Directors Dr Claire Francis and Hannah May - a few questions about their career journey. Q: Do you think it is important to celebrate International Women's Day? A: CF: Yes, for me it is an…

In March 2022, Dr Will Watson will be hanging up his laser pointer and commencing on new adventures as he starts his well earned retirement. Will has been a hugely valued member of the Scientific Update team since he joined in May 2000. During his 21+ years at the company he has trained more than…

I recall back in the late 1980’s, working for Smith Kline and French, reading a couple of articles in Tet. Letts. on biotransformations. I was intrigued, and a bit sceptical, that such transformations with enzymes would take place and lead to efficient large-scale processes. I had no experience or training in this area. My degree…

I was recently standing with several colleagues on the mezzanine level of a small batch manufacturing plant watching an operator charge LiOH-H2O into a reactor manway. Without warning we were all suddenly hit with a punch to the throat from inhalation of invisible caustic dust that had aerosolized during the charging, and we were forced…