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These Are Tri(azol)ing Times…. Great Chemistry- But Do Not Attempt on a Damp Day

Five-membered heterocyclic arenes account for a large portion of the heterocycles found in pharmaceuticals and bioactive molecules.1 Synthesis of heteroaryl halides and elaboration via metal catalysed cross coupling reactions- particularly with aliphatic amines- is, however, known to be challenging. These small heterocycles-particularly electron-rich systems- frequently coordinate to palladium, promoting catalyst deactivation via displacement of the supporting

One Functional Group, So Many Functions

The complex machinery required to take a drug through development and regulatory approval can be as arduous as the discovery of the molecule itself. In recent times the demand for COVID-19 drugs has added to the pressure to expedite this process in record time and several organizations working in the small molecule arena have met

Not a Dry Eye in the House

Yesterday I glanced through the list of drugs approved by the FDA in Q2 2023. One in particular, Miebo,1 -developed by Bausch and Lomb- made me sit up and stare. The compound is a partially fluorinated alkane (1-(Perfluorohexyl)octane, Figure 1) and is administered directly into the eye as a neat, anhydrous liquid to treat dry

Hey Phenol- Everyone has their Cross to Bear

Tert-butyl phenols are important commodity chemicals, with annual production exceeding 120,000 t per annum. They have multiple industrial applications including agrochemicals, antioxidants- in particular 2,6-di-tert-butyl-4- methylphenol (BHT, Figure 1), foods, flavours and fragrances and pharmaceuticals.1 BHT in particular, used as an antioxidant in polymers and oils and prepared by reaction of p-cresol with isobutylene in

The Germanes Have It

A couple of weeks ago I attended the 20th annual Bristol Synthesis Meeting at the Victoria rooms in Bristol, UK.1 Always an excellent event, and this one was no exception. I was intrigued by a presentation given by Franziska Schoenebeck from the University of Aachen, Germany on the application of organogermanes in cross coupling chemistry.

Ant Music

I don’t usually post articles on total synthesis. Their beauty often speaks for itself. However, a recent paper by Zhang and co-workers started me on a trip down memory lane. The paper describes a short, elegant route into the core 1-azabicyclo[4.3.0]nonane structure of the Indolizidine alkaloids (figure 1).1 Together with the structurally related pyrrolizidines (1-azabicyclo[3.3.0]octane),

Sodium Azide-Sonic Boom Boy

Last week I was in Madrid running our chemical development and scale up course. I met a great group of people, one of whom worked at Dynamit Nobel. During a coffee break we struck up a conversation about (of all things) azides, in particular sodium azide. Fairly quickly we both discovered that we had no

To Deprotect and Serve

Several weeks ago I did my annual analysis of the synthetic routes used to prepare small molecule drugs approved by the FDA in the preceding year, obviously in this case 2022.1 I  hope those of you who have seen the presentation found it as interesting to watch as I found to put it together. One

Triphenylphosphine Oxide- Waste Not, Want Not

Love it or hate it, triphenylphosphine oxide (TPPO, Figure 1) is something we all encounter at some point during our chemistry careers. Most of the time it’s just a by-product from well-established and widely used process such as the Mitsunobou, Wittig, Staudinger, Appel and Corey-Fuchs reactions.1 I remember having a vial full of the white,

A Mild Method for Dehydration of a Base-Sensitive Primary Amide- Toward a Key Intermediate in the Synthesis of Nirmatrelvir

Nirmatrelvir, the active ingredient of the Pfizer drug Paxlovid (Figure 1), is an inhibitor of the SARS-CoV-2 main protease enzyme.1 A key transformation- the final synthetic step in the synthesis of Nirmatrelvir- is dehydration of a primary amide (Figure 2).The amide starting material is prepared by reaction of the corresponding ester with ammonia.2 Various methods

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