Our laboratory recently synthesized a compound suspected to be N-Nitroso Finerenone. Attached are the MSS and HNMR.
Welcome everyone to discuss…
Dear Cato,
if your concern is the validity of the material, the 1H-NMR is a very minor information, specially if presented with no assignment table of the protons.
Usually 2-D NMRs are used in those cases, specially HSQC.
At least, the NMR of the Finerenone should be also shared in order to prove, with the comparison, that the -NH group is not anymore presented on the target molecule.
Furthermore, no MS spectra is identified.
Personally, i consider the synthesis of N-nitrosofinerenone very difficult, as the negative charge of the targeted nitrogen is strongly delocalized due to the resonance with the aromatic ring and the carbonyl moiety of the amide group,
Kind regards
Christos
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I was once under the impression that the synthesis of this nitrosamine impurity was not feasible.
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In my opinion, the nitrosation should lead to a aromatic ring, like it happens for dihydropyridine calcium channel blockers (Amlodipine and others similar APIs).
If my supposition is right, the main product should be this:
This impurity is available from many vendors, so you could easily verify if the structure is the same.
kind regards
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I agree with your point of view, but the tricky part is that the FDA has included this so-called nitrosamine, N-Nitroso Finerenone, in its list.
this does not mean necessarily that its synthesis is feasible. The example of N-nitroso ticagrelor, which is still present in the Appendix-1 of the relevant guideline of EMA, when its known that it cannot be synthesized more than one year ago, is very characteristic.
Furthermore, please note that as the N-nitrosofinerenone is included in the table 1 of the guideline which is for ‘‘FDA Recommended AI Limits for Certain Hypothetical NDSRIs and Other Identified Nitrosamine Impurities’’, is probably also this limit to be just hypothetical.
thanks
we also tried this and observed entirely cylclized product. The same happened with amlodipine too. refer this document for further clarity on this type moeties
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thanks you for your elaboration
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