The pyridyl group has been extensively employed to direct transition-metal-catalyzed C–H activation reactions in the past half-century. The typical cyclic transition states involved in these cyclometalation processes have only enabled the activation of ortho-C–H bonds. Here, we report that pyridine is adapted to direct meta-C–H activation of benzyl and phenyl ethyl alcohols through engineering the distance and geometry of a directing template. This template takes advantage of a stronger σ-coordinating pyridine to recruit Pd catalysts to the desired site for functionalization. The U-shaped structure accommodates the otherwise highly strained cyclophane-like transition state. This development illustrates the potential of achieving site selectivity in C–H activation via the recognition of distal and geometric relationship between existing functional groups and multiple C–H bonds in organic molecules.

A novel approach to hemiaminal synthesis via palladium-catalyzed C-N coupling with chiral bisphosphine mono-oxides is described. This efficient new method exhibits a broad scope, provides a highly efficient synthesis of HCV drug candidate elbasvir, and has been applied to the synthesis of chiral N,N-acetals.

Weakly Interacting Massive Particles (WIMPs) are the candidates of dark matter in our universe. Up to now any direct interaction of WIMP with nuclei has not been observed yet. The exclusion limits of the spin-independent cross section of WIMP-nucleon which have been experimentally obtained is about 10 −7 pb at high mass region and only 10 −5 pb at low mass region. China Jin-Ping underground laboratory CJPL is the deepest underground lab in the world and provides a very promising environment for direct observation of dark matter. The China Dark Matter Experiment (CDEX) experiment is going to directly detect the WIMP flux with high sensitivity in the low mass region. Both CJPL and CDEX have achieved a remarkable progress in recent two years. The CDEX employs a point-contact germanium semi-conductor detector PCGe whose detection threshold is less than 300 eV. We report the measurement results of Muon flux, monitoring of radioactivity and Radon concentration carried out in CJPL, as well describe the structure and performance of the 1 kg PCGe detector CDEX-1 and 10kg detector array CDEX-10 including the detectors, electronics, shielding and cooling systems. Finally we discuss the physics goals of the CDEX-1, CDEX-10 and the future CDEX-1T detectors.

Doravirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) currently in phase III clinical trials for the treatment of HIV infection. Herein we describe a robust kilo-scale synthesis for its manufacture. The structure and origin of major impurities were determined and their downstream fate-and-purge studied. This resulted in a redesign of the route to introduce the key nitrile functionality via a copper mediated cyanation which allowed all impurities to be controlled to an acceptable level. The improved synthesis was scaled to prepare ∼100 kg batches of doravirine to supply all preclinical and clinical studies up to phase III. The synthesis affords high-quality material in a longest linear sequence of six steps and 37% overall yield.

The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions. ■ RESULTS AND DISCUSSIONSynthesis of Triflate 4. Pyridyl aldehyde 5 was previously prepared on gram scale in 5 steps from picoline derivative 9. 6 A

Development of a convergent synthesis of omarigliptin (MK-3102) suitable for commercial manufacture is described. The target molecule is assembled through a diastereoselective reductive amination of a highly functionalized pyranone with a mesylated pyrazole followed by deprotection of a Boc group. The synthesis of the pyranone relies on three Ru-catalyzed reactions, 1) a DKR reduction of a rac-α-aminoketone to set the two contiguous stereogenic centers, 2) a cycloisomerization of a bis-homopropargylic alcohol to a dihydropyran, and finally 3) a Ru-catalyzed oxidation of a pyranol to the desired pyranone. A regioselective synthesis of an N-Boc-1-mesyl pyrazole fragment was achieved via a base promoted mesyl group isomerisation to afford 30:1 selectivity. A highlight of the endgame process development is telescoping a Boc deprotection and reductive amination followed by direct crystallization of the penultimate from the reaction mixture. This avoids handling of an unstable, mutagenic 1-mesylpyrazole BSA salt used in the earlier multi-kilogram deliveries, and improved the overall diastereoselectivity and efficiency of the route.

Verubecestat is an inhibitor of β-secretase being evaluated for the treatment of Alzheimer's disease. The first-generation route relies on an amide coupling with a functionalized aniline, the preparation of which introduces synthetic inefficiencies. The second-generation route replaces this with a copper-catalyzed C-N coupling, allowing for more direct access to the target. Other features of the new route include a diastereoselective Mannich-type addition into an Ellman sulfinyl ketimine and a late-stage guanidinylation.

Abstract. Jinping Underground lab for Nuclear Astrophysics (JUNA) will take the advantage of the ultralow background in Jinping underground lab, high current accelerator based on an ECR source and highly sensitive detector to study directly a number of crucial reactions to the hydrostatic stellar evolution for the first time at their relevant stellar energies. In its first phase, JUNA aims at the direct measurements of 25 Mg(p,γ) 26 Al, 19 F(p,α) 16 O, 13 C(α,n) 16 O and 12 C(α,γ) 16 O. The experimental setup, which include the accelerator system with high stability and high intensity, the detector system, and the shielding material with low background, will be established during the above research. The current progress of JUNA will be given. Article available at