During the N-Nitroso Ticagrelor synthesis, we encountered that no N-Nitrosation actually took place, and rather formation of some other NO-aduct (having the same Mass) has been isolated.
However, there are several companies that offers N-Nitroso Ticagrelor and what a surprise, N-Nitroso Ticagrelor have already its own CAS no. 2476859-55-7.
How exiting was, when I today came across online available document from MSN labs, where the MSN team experienced exactly the same issue; and describes proposed mechanism of Ticagrelor nitrosation, including cyclopropyl ring-opening, C-nitrosation followed by cyclization leading to 4,5-Dihydroisoxasole Derivate:
https://www.msnlabs.com/docs/scientific/TICAGRELOR_IMPURITY.pdf
Have you experienced the same?
We are working on synthesis of some ticagrelor nitrosamines derivatives…
will share our experience soon. thanks for the update
Interesting mechanism!
If synthesis proves impossible, this falls into the same bucket as the dipines - nitrosamines that would theoretically be category 5 but in practice do not form thus are not a concern at all. Anecdotally, something similar to your experience with contract manfacturers has also occured - a product is available claiming to provide nitroso-amlodipine, but upon delivery the compound proved to be something else…
See the current thread on the dipines for more discussion.
dipines do not form nitroso on the piperidine nitrogen , under nitrosation conditions they aromatize to form corresponding pyridine analogs… this is our practical experience…