The Lab Notes

The scheme below shows the synthesis of a late-stage intermediate towards PF-06826647, a compound identified by Pfizer as a potent and selective tyrosine kinase 2 (TYK-2) inhibitor that has entered phase 2 clinical trials for the treatment of autoimmune diseases. Can you identify intermediates A, B and D? Answers and a reference will be posted…

Last month I posted a scheme for the synthesis of a late-stage intermediate towards AZD9833, a compound identified by AstraZeneca as a selective estrogen receptor degrader (SERD) and antagonist that is currently in phase 2b clinical trials for the treatment of ER+ breast cancer. I asked if you could identify reagents or intermediates A-C. Below are…

It’s not often that drug molecules find themselves on the reagent shelf alongside materials that may have been used to assemble them. The prince and the pauper so to speak. In 2019 Paul Hergenrother from the University of Illinois published a paper in Angewandte Chemie claiming a diazomethane surrogate that was a commercially available, weighable, solid:…

A couple of interesting papers published recently on aryl iodination. I sure I don’t need to reiterate how useful iodinated intermediates are in synthesis- most significantly their heightened reactivity in metal catalysed cross coupling chemistry,1 and, more recently their application as organocatalysts in hypervalent iodine chemistry.2 As is common in synthetic science, the intermediates you…

In June of 1886 (26th to be precise) the French chemist Henri Mossian passed an electric current through a solution of KHF2 in anhydrous HF and became the first person to generate fluorine. Rather him than me. But he did, quite rightly, win a Nobel prize for his efforts in 1905. [caption id="attachment_11731" align="alignnone" width="422"]…

The scheme below shows the synthesis of a late-stage intermediate towards AZD9833, a compound identified by AstraZeneca as a selective estrogen receptor degrader (SERD) and antagonist that is currently in phase 2b clinical trials for the treatment of ER+ breast cancer. Can you identify reagents or intermediates A, B and C? Answers and a reference…

Last month I posted a scheme from showing Oppolzer’s synthesis of racemic Lysergic acid and asked if you could identify reagents or intermediates G, I, and H. Below are the answers! You can read more here in the full reference: W. Oppolzer et al, Helv. Chim. Acta 1981, 64, 478–481  

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In 1981 Oppolzer published a short, racemic synthesis of Lysergic acid. Below is a scheme of the early steps in the synthesis. Can you identify reagents or intermediates G, I and H? Answers and a reference will be posted in late June, along with another problem. Enjoy!  

Last month I posted a scheme from a paper by a team from Merck describing the synthesis of a soluble guanylate cyclase (cGC) stimulator of interest for the treatment of hypertension and asked if you could identify reagents or intermediates B, F, and the target compound H. Below are the answers! You can read more here in…