A microplate-based assay to rapidly identify adsorbents suitable for removing process impurities is described. A solution containing both product and impurity is added to a number of wells, each containing a small amount of a candidate adsorbent. After equilibration, analysis of the supernatant solution allows one to determine the extent of adsorption of both product and impurity. Fast analysis techniques such as flow injection analysis LC-MS or the use of colorimetric indicators allows rapid identification of the most selective adsorbents for a given separation problem.

A facile preparation of enantiopure ethyl (1S,5S,6S)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate is described. The key feature of the synthesis involves copper-catalyzed enantioselective intramolecular cyclopropanation of a diazoketone to form endo-fluorocyclopropane in a single operation. Removal of a problematic chloroketone impurity using a reactive resin treatment enabled a high throughput enantiopurity upgrade by chiral HPLC. The development of a scalable synthesis of is presented, including details of the selection of catalyst and ligand optimization, incorporation of a reactive resin treatment and selection of chiral HPLC media and conditions.

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The development of potent gamma-secretase inhibitors having substituted heterocycles attached to a benzobicyclo[4.2.1]nonane core is described. This work led to the identification of [6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(4-fluorophenyl)-1-methylpyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide (16), which has excellent in vitro potency (0.06 nM) and which reduced amyloid-beta in APP-YAC mice with an ED(50) of 1 mg/kg (po). 16 had a good pharmacokinetic profile in three preclinical species.

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A numerical investigation of the heat transfer enhancement through fins using the Ansys Mechanical solver is presented. Results are given for a uniform fin with elliptical cross-sections and uniform heat flux applied on its base while heat is dissipated to its surroundings by convection from both its lateral surface and tip. The peak temperature at the base of the fin is used to evaluate the thermal performance. Ansys Mechanical solver is automated using Python scripting to run 792 simulations for various materials, fin lengths, and ratios between the minor and major axes of the elliptical cross-sectional shape for both cases of natural and forced convection. The use of the original automated numerical procedure significantly decreases the computational time and the user intervention. It was found that the thermal performance is improved by increasing the length of the fin, using a material with higher thermal conductivity, or having a ratio between the minor and major axes of the ellipse that is farther from unity. Forced convection gives better thermal performance compared to natural convection.

This paper presents an original numerical study for the optimization of the steady laminar fluid flow and heat transfer in a two-dimensional corrugated channel with a bottom heated wall and an upper periodically corrugated wall. A python code is used to automate Ansys Fluent and to run the simulation for various shapes of the corrugated wall given by a polynomial function. The optimal values for the coefficients of the fifth-order polynomial defining the shape of the upper wall are determined. The average Nusselt number and the Reynolds number are plotted as a function of two geometrical coefficients. A correlation for the average Nusselt number as a function of the Reynolds number for this flow is proposed. It was found that there exist optimal parameters of the corrugated channel for which the average Nusselt number is higher than that of parallel walls due to the development of secondary flows.

Preparative chromatography was used to overcome the difficult selectivity challenge of accessing a single isomer of a mono tertbutyldimethylsilyl (TBDMS) derivative of an unsymmetrical diol. Chromatographic purification allowed rapid purification of more than 10 kg of the desired intermediate from the statistical mixture of undesired mono-TBDMS, bis-TBDMS, and very strongly retained, unreacted starting material. A noteworthy injection cycle strategy of performing three injections, then desorbing the accumulated strongly bound diol starting material with a strong solvent wash was employed in the separation.