Synthesis of novel serotonergics and other N-alkylamines using simple reductive amination using catalytic hydrogenation with Pd/C

Formation of N-alkylated α-methyltryptamine derivatives (2) was accomplished by simple reductive amination of amine (1) with ketones using catalytic hydrogenation conditions (3 atm H₂ and 10% Pd on carbon). This method was also applied to other primary and secondary amines using ketones and aldehydes.     

Syntheses of aza and fluorine-substituted 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-ones

A practical and expedient synthesis of the title compounds is described. They were prepared by Stille reaction of nitro halopyridines 4 or nitro fluro-halobenzenes 10, followed by Michael addition of tert-butyl 4-aminopiperidine-1-carboxylate to the resulting activated vinyl compounds 5 and 11, hydrogenation (-NO₂→-NH₂), cyclic urea formation, Boc removal, and HCl salt formation. However, N3 and F1 analogs could not be made by this general strategy. Activated vinyl compounds 5a and 5d when reacted with tert-butyl 4-aminopiperidine-1-carboxylate did not stop at the desired Michael addition stage; but proceeded to produce azaindolines 8 and 9. Michael addition did not occur to compound 11d; instead, the fluorine atom was displaced.     

Novel intramolecular diels-alder reactions with alkynylthio derivatives of 1,2,4-triazines. New routes to thieno[2,3-b]pyridines and thieno[2,3-c]pyridines.

S-Alkylation of 1,2,4-triazine-6-thiones with 4-iodobutyne, followed by oxidation to the sulfoxide and intramolecular cycloaddition (at room temperature),gives 2,3-dihydrothieno[2,3-$\text{c}$]pyridines, which are readily dehydrated with acetic anhydride to thieno[2,3-$\text{c}$]pyridines. The same series of reactions carried out on 1,2,4-triazine-3-thiones leads to thieno[2,3-$\text{b}$]pyridines.     

Channeling chaos by building barriers

Chaotic diffusion often represents a severe obstacle for the setup of experiments, e.g., in fusion plasmas or particle accelerators. We present a complete test of a method of control of Hamiltonian chaos, with both its numerical test and its first experimental realization on a paradigm for wave-particle interaction, i.e., a travelling wave tube. The core of our approach is a small apt modification of the system which channels chaos by building barriers to diffusion. Its experimental realization opens the possibility to practically achieve the control of a wide range of systems at a low additional cost of energy.     

Experimental observation of nonlinear synchronization due to a single wave

A test electron beam is propagated in a specially designed traveling wave tube. It interacts with a nonresonant wave, and its energy distribution is recorded at the tube output. We report the direct experimental observation of the spatially periodic electron velocity bunching, and of a nonlinear effect on the electron velocity modulation: the synchronization of the particles with the wave responsible for Landau damping in plasma physics. The results are explained by second order perturbation theory in the wave amplitude.     

Characterization of the in vitro atropisomeric interconversion rates of an endothelin A antagonist by enantioselective liquid chromatography

Substituted biphenyl I (BMS-207940), a selective antagonist of the endothelin A (ETA) receptor, has been proposed for the treatment of congestive heart failure. The structure of I possesses a stereogenic axis due to the hindered rotation about the biphenyl bond in the presence of its large ortho-substituents. As a result, I exhibits atropisomerism in which two nonplanar, axially enantiomers exist, which will be generically referred to as isomers A and B. Within the pharmaceutical industry, both from a scientific and regulatory point of view, characterization of enantiomeric drugs has become an important step in the development process. To investigate the configurational stability of I atropisomers, normal phase enantiomeric LC with tandem UV and laser polarimetric detection was used under pseudo-physiological conditions: first in a simple aqueous medium at 37 degrees C, and then in human serum at 37 degrees C. Kinetic studies indicated that the half-life of I enantiomerization in an aqueous medium at 37 degrees C was ca. 15 h. Enantiomerization of I atropisomers was greatly accelerated in the presence of human serum and human serum albumin, and the rate of enantiomerization depended on the concentration of I. The sera-concentration-dependent enantiomerization behavior of I strongly suggests a restricted site-specific substrate/I interaction mechanism. It was therefore demonstrated that atropisomeric interconversion studies for the compound studied required consideration of temperature, presence of plasma proteins, and drug concentration to account for the kinetic data.     

ChemInform Abstract: Synthesis and Single Crystal Structure of Sodium Octahydrotriborate,NaB3H8.

The title compound is prepared by a modified synthesis involving the reduction of BH₃·THF with Na dispersed on silica gel (-10 °C), removal of THF, and extraction by Et₂O.