Direct Multi-Deuterium Labelling of Pirtobrutinib
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00587960" target="_blank" >RIV/61388963:_____/24:00587960 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/24:10483011
Result on the web
<a href="https://doi.org/10.1002/jlcr.4117" target="_blank" >https://doi.org/10.1002/jlcr.4117</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/jlcr.4117" target="_blank" >10.1002/jlcr.4117</a>
Alternative languages
Result language
angličtina
Original language name
Direct Multi-Deuterium Labelling of Pirtobrutinib
Original language description
Herein, we demonstrate an efficient method for multi-deuterium labelling of pirtobrutinib-a Bruton's tyrosine kinase inhibitor recently approved by the FDA-using a straightforward hydrogen isotope exchange (HIE) reaction. A remarkably high level of deuterium incorporation was achieved using an excess of a Kerr-type iridium catalyst. The key factor in the significant deuterium labelling was the decision to employ a deuterium uniformly labelled solvent, chlorobenzene-d5, at an elevated temperature. Virtually, no d0-d3 species were detected, with only traces of d4-d5 isotopomers (<5%) observable in the mass spectrum of pirtobrutinib-d8, fulfilling requirements for stable isotope-labelled internal standard. The labelled compound-mainly consisting of isotopomers d6-d9 at 82.4% of the total abundance-was isolated in a high yield (73%) and purity (99%). Noteworthy, fluorine group acting as a directing group was observed for the first time. Significant incorporation of deuterium in ortho-positions, exceeding 87%, was observed. Interestingly, chlorinated solvent used in the HIE reactions was non-specifically deuterated yielding up to 0.42 deuterium per chlorobenzene molecule even at an exceptionally low iridium catalyst loading of 4.17*10-2mol%.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Labelled Compounds and Radiopharmaceuticals
ISSN
0362-4803
e-ISSN
1099-1344
Volume of the periodical
67
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
314-323
UT code for WoS article
001272260800001
EID of the result in the Scopus database
2-s2.0-85198387545