Cryogen-free 400-MHz nuclear magnetic resonance spectrometer as a versatile tool for pharmaceutical process analytical technology.

The discovery of new ceramic materials containing Ba-La-Cu oxides in 1986 that exhibited superconducting properties at high temperatures in the range of 35 K or higher, recognized with the Nobel Prize in Physics in 1987, opened a new world of opportunities for nuclear magnetic resonance (NMRs) and magnetic resonance imaging (MRIs) to move away from liquid cryogens. This discovery expands the application of high temperature superconducting (HTS) materials to fields beyond the chemical and medical industries, including electrical power grids, energy, and aerospace. The prototype 400-MHz cryofree HTS NMR spectrometer installed at Amgen's chemistry laboratory has been vital for a variety of applications such as structure analysis, reaction monitoring, and CASE-3D studies with RDCs.

Synthesis of Substituted Pyridines via Formal (3+3) Cycloaddition of Enamines with Unsaturated Aldehydes and Ketones.

An organocatalyzed, formal (3+3) cycloaddition reaction is described for the practical synthesis of substituted pyridines. Starting from readily available enamines and enal/ynal/enone substrates, the protocol affords tri- or tetrasubstituted pyridine scaffolds bearing various functional groups. This method was demonstrated on a 50 g scale, enabling the synthesis of 2-isopropyl-4-methylpyridin-3-amine, a raw material used for the manufacture of sotorasib.

Nitration of Aryl Boronic Acids Using Fuming Nitric Acid.

The nitration of aryl boronic acid derivatives has been developed using fuming nitric acid as the nitrating agent. This facile procedure provides efficient and chemoselective access to a variety of aromatic nitro compounds. While several activating agents and nitro sources have been reported in the literature for this synthetically useful transformation, this report demonstrates that these processes likely generate a common active reagent, anhydrous HNO.

Isotopically Directed Symmetry Breaking and Enantioenrichment in Attrition-Enhanced Deracemization.

The evolution of homochirality via attrition-enhanced deracemization (AED) of enantiomorphic solids is carried out using molecules that differ only in the isotopic composition of a phenyl group positioned remote from the chiral center. Enantioenrichment consistently favors the enantiomorph containing a deuterated phenyl group over the protio or C version, and the protio version is consistently favored over the C version. While these isotopic compounds exhibit identical crystal structures and solubilities, the trend in deracemization correlates with melting points.

Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst.

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6-19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst.

Crystal structure of 1-methylimidazole 3-oxide monohydrate.

1-Methylimidazole 3--oxide (NMI-O) crystallizes as a monohydrate, CHNO·HO, in the monoclinic space group 2 with ' = 2 (mol-ecules and ). The imidazole rings display a planar geometry (r.m.

Highly efficient and selective phosphorylation of amino acid derivatives and polyols catalysed by 2-aryl-4-(dimethylamino)pyridine-N-oxides--towards kinase-like reactivity.

The chemoselective phosphorylation of hydroxyl containing amino acid derivatives and polyols by phosphoryl chlorides catalyzed by 2-aryl-4-(dimethylamino)pyridine-N-oxides is described.

Alternative synthetic tools to phospho-specific antibodies for phosphoproteome analysis: progress and prospects.

Signal transduction cascades in living systems are often controlled via post-translational phosphorylation and dephosphorylation of proteins. These processes are catalyzed in vivo by kinase and phosphatase enzymes, which consequently play an important role in many disease states, including cancer and immune system disorders. Current techniques for studying the phosphoproteome (isotopic labeling, chromatographic techniques, and phosphospecific antibodies), although undoubtedly very powerful, have yet to provide a generic tool for phosphoproteomic analysis despite the widespread utility such a technique would have.