Facile and Scalable Methodology for the Pyrrolo[2,1-f][1,2,4]triazine of Remdesivir

<div> <div> <p>Pyrrolo[2,1-f][1,2,4]triazine (<b>1</b>) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound<b> 1</b> was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine <b>1</b> was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.</p> </div> </div> <br>

Facile and Scalable Methodology for the Pyrrolo[2,1-f][1,2,4]triazine of Remdesivir

<div> <div> <p>Pyrrolo[2,1-f][1,2,4]triazine (<b>1</b>) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound<b> 1</b> was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine <b>1</b> was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.</p> </div> </div> <br>

Process Development and Synthesis of Process-Related Impurities of an Efficient Scale-Up Preparation of 5,2′-Dibromo-2,4′,5′-Trihydroxy Diphenylmethanone as a New Acute Pyelonephritis Candidate Drug

Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone (LM49-API), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of LM49-API and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of LM49-API. Its finalized preparation process was further validated at 329–410 g scale-up production in 53.4–57.1% overall yield with 99.95–99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production. LM49-API-imC and LM49-API-imX were identified as the main single impurities in LM49-API, with the content controlled to be less than 0.03%.

A simple, sensitive, high-resolution, customized, reverse phase ultra-high performance liquid chromatographic method for related substances of a therapeutic peptide (bivalirudin trifluoroacetate) using the quality by design approach

Among all chemical sameness characterization tests of Therapeutic Peptides (TPs), one of the most significant and challenging aspects is to demonstrate comparable impurity profiles (both qualitative & quantitative) between a generic product and reference listed drug (RLD).