Hiray Pharma Solutions Announces Technical Milestones in the Advanced Process Development of Orforglipron Manufacturing Chain

Jingmen, China, March 2026 — Hiray Pharma Solutions Ltd., a leading global technology-driven CDMO and API manufacturer, today disclosed significant technical milestones in the process optimization of Orforglipron, a high-potential oral non-peptidic GLP-1 receptor agonist. By integrating frontier organometallic research with advanced industrial engineering, Hiray has successfully overcome critical barriers in both manufacturing cost-efficiency and stereochemical precision for the Orforglipron API and its key structural fragments.

Strategic Integration of Fundamental Research and Industrial Application

The technological trajectory of Hiray Pharma Solutions is anchored by high-level academic collaboration. Under the scientific guidance of Professor Wenbo Liu (Chief Scientific Advisor and recent Nature Communications author), Hiray has bridged the gap between fundamental organometallic methodologies and scalable pharmaceutical manufacturing. Professor Liu’s recent breakthroughs in catalyst-controlled stereodivergent synthesis have directly empowered Hiray’s R&D team to innovate the complex molecular assembly of Orforglipron with unprecedented efficiency.

Sustainability and Cost Leadership: The Copper-Catalyzed Innovation (CAS: 2212021-40-2)

In the synthesis of the critical Orforglipron intermediate, (4-Fluoro-3,5-dimethylphenyl)hydrazine hydrochloride, Hiray’s technical team has implemented a paradigm shift in catalytic methodology, transitioning from traditional precious metal catalysis to a sustainable copper-based system.

· Catalytic Optimization: The team replaced the costly palladium-acetate/Xantphos system with a significantly more economical copper bromide (CuBr2) catalyst in combination with a proprietary redox-active pyrrolyl hydrazide ligand (L).

· Enhanced Process Stability: By strategically employing Cu(II) instead of Cu(I), Hiray successfully bypassed the common industrial failure point of catalyst oxidation poisoning, ensuring high reliability in large-scale production.

· Quantitative Yield & Purity: Optimized DMSO-based reaction parameters achieved a total yield of 80%. By refining the stoichiometry of hydrazine hydrate to 7.0 eq, product HPLC purity was elevated from 86.37% to 94.35%, while reducing starting material residue to a negligible 0.14%.

Stereochemical Precision: Suppressing the Diastereomeric Barrier in HR2331-M04/M06

The construction of the HR2331-M06 fragment presents formidable challenges in stereocontrol, specifically regarding the suppression of the undesired ent-M04 diastereomer during the allylic alkylation of intermediate HR2331-M04.

Hiray’s R&D team conducted deep-dive mechanistic investigations into the Schlenk equilibrium and solvent dependency of the Turbo Grignard reagent (i-PrMgCl·LiCl). Key technical achievements include:

· Conformational Stabilization: To counter the free rotation of the α-carbonyl group and deprotonation of the indole N-H moiety, the team employed a specialized protection strategy (Boc/TMS groups) and precise cryo-regulation at -40°C.

· Exacting Impurity Control: These refined protocols consistently maintain the critical ent-M04 impurity level below 1.5%, fulfilling the rigorous stereochemical requirements for the final Orforglipron API.

About Hiray Pharma Solutions

Hiray Pharma Solutions Ltd. is a technology-driven API and CDMO platform and a core subsidiary of Wuhan Hiteck Biopharmaceutical Co., Ltd.. Located in the Jingmen Chemical Recycling Industrial Park, Hubei Province, the company’s 310-acre production base features 7 GMP workshops (3 multi-functional and 4 commercialization) and 6 non-GMP workshops. With reactor capacities ranging from 30L to 10,000L, Hiray supports complex chemical processes, including high-pressure hydrogenation and extreme temperature reactions. As a specialized supplier of the Orforglipron intermediate series, Hiray leverages intelligent manufacturing and green chemistry to provide sustainable, high-quality CDMO services to global Big Pharma and Biotech innovators.