Orforglipron Intermediate M-4

Orforglipron Intermediate M-4 (HR2331-M04) is a key chiral intermediate in the synthesis of the oral GLP-1 receptor agonist Orforglipron. It serves as the source module for constructing the (S)-tetrahydropyran ring core scaffold in M-6 and the final product. Its stereochemistry and purity directly determine the optical purity and pharmacological activity of subsequent intermediates and the API. Diastereomeric impurities (such as ent-M04) must be strictly controlled to within 1.5%.

Appearance: White to off-white crystalline powder. Chiral purity and impurity content affect the powder's crystal form and flowability.

Solubility: Easily soluble in DCM, THF, and DMF; slightly soluble in n-hexane, water, and diethyl ether; purification is typically achieved through column chromatography or ethyl acetate/n-hexane recrystallization.

Stability: Store in a sealed container, protected from light, and in a dry place below 25°C, avoiding high temperatures and humid environments; the Evans auxiliary group is sensitive to strong acids and bases, requiring protection against hydrolysis and racemization; shelf life is approximately 12 months.

Key Quality Control Indicators:

Chemical Purity: ≥99.0% (HPLC area normalization method)

Diastereoisomer (ent-M04): ≤1.5% (Chiral HPLC/SFC)

Moisture Content: ≤0.5% (Karl Fischer method)

Heavy Metals: ≤10 ppm (ICP-MS)