4 research outputs found
Promotion of a Ti-Mediated Mannich Reaction by a Proton Source
Low
temperature NMR studies revealed that a diastereoselective
Mannich reaction between a phenyl oxazolidone-derived titanium enolate
and an aromatic aldimine was found to occur only after introduction
of a proton source. While various protic additives could be used to
promote the transformation, the best results were obtained using AcOH
to afford the corresponding Mannich products in high diastereoselectivities
and yields
Promotion of a Ti-Mediated Mannich Reaction by a Proton Source
Low
temperature NMR studies revealed that a diastereoselective
Mannich reaction between a phenyl oxazolidone-derived titanium enolate
and an aromatic aldimine was found to occur only after introduction
of a proton source. While various protic additives could be used to
promote the transformation, the best results were obtained using AcOH
to afford the corresponding Mannich products in high diastereoselectivities
and yields
The Discovery of Quinoxaline-Based Metathesis Catalysts from Synthesis of Grazoprevir (MK-5172)
Olefin metathesis
(OM) is a reliable and practical synthetic methodology
for challenging carbon–carbon bond formations. While existing
catalysts can effect many of these transformations, the synthesis
and development of new catalysts is essential to increase the application
breadth of OM and to achieve improved catalyst activity. The unexpected
initial discovery of a novel olefin metathesis catalyst derived from
synthetic efforts toward the HCV therapeutic agent grazoprevir (MK-5172)
is described. This initial finding has evolved into a class of tunable,
shelf-stable ruthenium OM catalysts that are easily prepared and exhibit
unique catalytic activity
Careful Navigation of the Crystallographic Landscape of MK-8970: AÂ Racemic Acetal Carbonate Prodrug of Raltegravir
MK-8970
is an acetal carbonate prodrug of raltegravir (Isentress).
This work presents the Merck team’s investigations into the
polymorphism of MK-8970, the thermodynamic relationship between the
discovered crystalline forms, and implementation of that knowledge
toward solving key processing challenges. MK-8970 was found to exist
in two enantiotropic polymorphs, with a crossover temperature of approximately
117 °C, as determined from solubility data. Form 2 of MK-8970,
the stable form at ambient temperature, was confirmed to be a true
racemic crystal form and not a conglomerate on the basis of single-crystal
X-ray structure data. In preparation for scale-up of MK-8970, form
control was established by mapping out solubility curves for the relevant
crystalline forms in ethyl acetate as a function of temperature. Lastly
an investigation of the relative solubilities of MK-8970 and a troublesome
imidate impurity identified improved solvent systems for maximizing
rejection of this impurity while avoiding significant yield losses