The development of a process for appending the oxalyl amide side chain to the azaindole core of the HIV-attachment inhibitor BMS-663068 is described. A Friedel–Crafts acylation installed the oxalyl ester, which was subsequently hydrolyzed and amidated with a benzoyl piperazine. The development of the commercial route necessitated several key changes to the initial synthesis. For instance, in the original acylation process, nitromethane, a commonly used, but highly energetic cosolvent, was employed which was eventually replaced by catalytic tetra-n-butylammonium bisulfate to overcome gelling issues encountered during the reaction when nitromethane was omitted. It was further demonstrated that the amidation sequence could be relegated to a single-pot, homogeneous transformation through the use of the cost-effective coupling reagent diphenylphosphinic chloride. The above modifications have been utilized in multiple campaigns and reproducibly demonstrated on scales of up to 200 kg input.

中文翻译：

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HIV附着抑制剂BMS-663068的制备。第6部分。Friedel-Crafts酰化/水解和酰胺化

描述了将草酰酰胺侧链附加到HIV-附着抑制剂BMS-663068的氮杂吲哚核心上的方法的开发。Friedel-Crafts酰化反应安装了草酸酯，然后将其水解并用苯甲酰基哌嗪酰胺化。商业路线的发展需要对初始合成进行几个关键的改变。例如，在原来的酰化方法，硝基甲烷，通常使用的，但高能量的助溶剂中，采用其最终被催化四取代Ñ丁基硫酸氢铵克服了在省略硝基甲烷时反应过程中遇到的胶凝问题。进一步证明，通过使用成本有效的偶联剂二苯基次膦酰氯，可以将酰胺化序列降级为单锅均质转化。以上修改已在多个战役中使用，并在最大200千克输入磅的规模上可重复显示。