An approach to isolate first crystals for molecules prone to liquid‐liquid phase separation (LLPS) is described. In the absence of knowledge about the solubility of a hypothetical crystal, it is proposed to determine the LLPS phase boundary, then operate at a temperature of 2 °C above the LLPS to maximize the supersaturation with respect to a hypothetical crystalline phase and to avoid LLPS. The proposed approach, combined with a careful solvent and counterion selection based on molecular size, allowed isolating a crystalline salt that was elusive using high‐throughput screening. The crystalline salt displayed higher resistance to mechanical stress than the crystalline parent, allowing the progression of the molecule in the development pipeline.

中文翻译：

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易发生液相分离的物质的第一晶体的生成途径

描述了一种分离第一晶体的方法，该分子易于发生液相-液相分离（LLPS）。在不了解假设晶体的溶解度的情况下，建议确定LLPS相边界，然后在LLPS之上2°C的温度下操作，以最大程度地提高假设晶体相的过饱和度，并避免LLPS 。所提出的方法与基于分子大小的谨慎溶剂和抗衡离子选择相结合，可以分离出使用高通量筛选难以捉摸的结晶盐。结晶盐显示出比结晶母体更高的抗机械应力性，从而使分子在显影管线中得以发展。