In the past several decades, the experimental method has lent deep insights into economics. One area that has contributed is the experimental study of children, where advances as varied as the ...evolution of human behaviors that shape markets and institutions to how early life influences shape later life outcomes, have been explored. We first develop a framework for economic preference measurement that provides a lens into how to interpret data from experiments with children. Next, we survey work that provides general empirical insights within our framework and provide a comprehensive summary of experimental methods used with children. Finally, we provide 10 tips for pulling off experiments with children, including factors such as taking into account child competencies, causal identification, and logistical issues related to recruitment and implementation. We envision the experimental study of children as a high-growth research area in the coming decades as social scientists begin to more fully appreciate that children are active participants in markets who (might) respond predictably to economic incentives. (JEL C90, D11, D83, D91, J13, J16, Z13)
A review of reactions scaled in the GMP facilities at the Pfizer-Groton site was undertaken. Reactions were categorized into one of seven categories: carbon−carbon bond formation, carboxylic acid ...derivative interconversion, carbon−nitrogen bond formation, carbon−oxygen bond formation, red-ox, salt formation/resolution, and other. Reactions scaled from 1997 to 2002 were compared to chemistry scaled from 1985 to 1996 to look for changes in the nature of chemistry being scaled between the two time periods. Reactions were further subcategorized within those categories, and some interesting trends were noted.
A review of large-scale oxidations in the pharmaceutical industry is presented. Oxidation reactions are powerful tools to convert a position that is protected in a lower oxidation state to the ...desired functionality and for the functionalization of otherwise unfunctional positions.
Nirmatrelvir (PF-07321332, 1) is a selective, orally bioavailable inhibitor of SARS-CoV-2 2 Mpro. Development of an efficient synthesis of this molecule was critical for the rapid advancement of the ...compound from first synthesis to successful emergency use authorization in just 17 months. This paper provides an overview of the development of the commercial synthesis, with a focus on the supply chains for the three starting materials, which leveraged key synthetic studies from earlier protease research programs and/or commercial products.
A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations ...over a 12-step sequence. The dioxa-bicyclo3.2.1octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-d-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with l-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.
Increased erosion is a well‐known response after wildfire. To predict and to model erosion on a landscape scale requires knowledge of the critical shear stress for the initiation of motion of soil ...particles. As this soil property is temperature‐dependent, a quantitative relation between critical shear stress and the temperatures to which the soils have been subjected during a wildfire is required. In this study the critical shear stress was measured in a recirculating flume using samples of forest soil exposed to different temperatures (40°–550°C) for 1 hour. Results were obtained for four replicates of soils derived from three different types of parent material (granitic bedrock, sandstone, and volcanic tuffs). In general, the relation between critical shear stress and temperature can be separated into three different temperature ranges (<175°C; 175°C–275°C; >275°C), which are similar to those for water repellency and temperature. The critical shear stress was most variable (1.0–2.0 N m−2) for temperatures <175°C, was a maximum (>2.0 N m−2) between 175° and 275°C, and was essentially constant (0.5–0.8 N m−2) for temperatures >275°C. The changes in critical shear stress with temperature were found to be essentially independent of soil type and suggest that erosion processes in burned watersheds can be modeled more simply than erosion processes in unburned watersheds. Wildfire reduces the spatial variability of soil erodibility associated with unburned watersheds by eliminating the complex effects of vegetation in protecting soils and by reducing the range of cohesion associated with different types of unburned soils. Our results indicate that modeling the erosional response after a wildfire depends primarily on determining the spatial distribution of the maximum soil temperatures that were reached during the wildfire.
•Separation of non-polar and semi-volatile arene regioisomers without derivatization.•Utilization of high temperature gas chromatography with flame ionization detection.•Validation parameters ...included linearity, precision, accuracy, repeatability and sensitivity.•Broad range of applications where separation of isomers is required.
This paper describes the development and validation of a high temperature gas chromatography flame ionization detection (HTGC-FID) method for the purity evaluation of arene substituted regioisomers in a key starting material of a pharmaceutical candidate in Phase 3 studies. The chromatographic conditions of the method employ a (5%-phenyl)-methylpolysiloxane packed column (30m×0.25mm) at a constant flow of 1.0mLmin−1 with a gradient temperature program from 150°C to 400°C with injector and detector temperatures of 300°C and 340°C, respectively. The calibration curve for the desired product (r=0.9999) was assessed for five points in the range from approximately 1.0μgmL−1 to 40μgmL−1. The precision (% RSD) of the method was calculated for six replicate injections and found to be 0.81%. The limits of detection and quantitation were determined to be 0.06 and 0.20μgmL−1, respectively.
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