Rupanjali Prasad, Stefani Kocevska, Dimitri Skliar, Martha A. Grover, Ronald W. Rousseau
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引用次数: 0
Abstract
Characteristics of BMS-817399 that could influence the potential utility of the compound as an active pharmaceutical ingredient (API) have been explored. The compound exists as a monohydrate (Form 1) but is physically unstable as its crystal structure changes with variations in relative humidity and temperature. Thus, identifying a form that remains physically stable under fluctuating conditions of relative humidity was the objective of this work. Solubilities of Form 1 in ethanol, isopropanol, acetone, and acetonitrile were obtained using a Crystal16 apparatus, but recrystallization only occurred when the solvent was acetonitrile. X-ray diffraction (XRD) of solids obtained from recrystallization in the Crystal16 apparatus and from larger-scale experiments confirmed the existence of a new form (Form 2) of the compound. Solubilities of Form 2 were subsequently determined by using the Crystal16 apparatus. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed Form 1 as a monohydrate and showed that Form 2 is anhydrous. Dynamic vapor sorption was used to show that the water content of Form 1 varied with the relative humidity. Form 2 also became hygroscopic at elevated relative humidity, but XRD measurements confirmed that it exhibited physical stability.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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