文章预览
Org. Lett. 2021, 23, 5400 − 5404. DOI: 10.1021/acs.orglett.1c01725 ◆ A retrosynthetic analysis of MMV390048
points toward assembly of the triaromatic core through a series of
cross-coupling reactions mediated by palladium catalysis. ◆ Reaction of the electrophilic iminium salt
8 with a carbon centered nucleophile such as nitrile 9 would eliminate the need
for palladium crosscouplings altogether, the biaryl bonds are already present
in the starting material. ◆ We commenced our investigation by looking
toward economical construction of 5-bromo-2-trifluoromethylpyridine 12 en route
to the nitrile 9. ◆ The pyridine ring could instead be built
from ethyl 4,4,4-trifluoromethyl-3-aminocrotonate 10, by reacting it with 11
which is made from chloroacetic acid, DMF, POCl3, and hexafluorophosphoric acid ◆ We concluded our investigation by testing
the key tenet: that the two terminal aromatic subunits could be coupled with
simultaneous construction of the central aminopyridine ring and
………………………………
