Glecaprevir

China [CN]

Physical state: At room temperature, it is a white to light yellow crystalline powder, odorless, with moderate hygroscopicity (due to hydrochloride salt + secondary hydroxyl hydrogen bonding), requiring vacuum sealing to prevent moisture absorption;

Melting point: 178~183℃ (melting range ≤5℃; a melting range exceeding this indicates the presence of diastereoisomers/cis-double bond impurities), melting is accompanied by slight decomposition, and is a key indicator for initial assessment of configuration/purity;

Specific rotation: [α]D25 = +42° to +48° (c=1.0, methanol), the sole indicator for determining chiral configuration; deviation from this range indicates the presence of racemic mixture;

Solubility: Easily soluble in water (solubility at 25℃ ≈ 45g/L, a core advantage of the hydrochloride salt), easily soluble in methanol, ethanol, DMSO, DMF, slightly soluble in ethyl acetate, tetrahydrofuran, insoluble in dichloromethane, toluene, n-hexane (water solubility is suitable for subsequent aqueous phase/semi-synthetic processes);

Dissociation constant: Hydrochloride salt pKa ≈ 1.8 (amino group), pKa ≈ 4.2 (proline ring imine), pKa ≈ 9.8 (secondary hydroxyl group), the aqueous solution is strongly acidic (pH 1.5~2.5), adding alkali (NaHCO3) to adjust the pH to 5~6 can liberate the basic product and cause precipitation;

Stability:

Stable for ≥24 months when stored dry and sealed at room temperature (2~8℃) without degradation; storage at room temperature (25℃) for ≤7 days is acceptable, but long-term storage at room temperature will lead to moisture absorption and double bond isomerization;

Stable to acids (pH 1~7) and conventional reducing agents, under alkaline conditions (pH>8) double hydrolysis occurs: ester hydrolysis to carboxylic acid and slight cleavage of the ether bond;

Double bond configuration: The E-form difluoroolefin is the thermodynamically stable configuration, but under ultraviolet light/high temperature (>100℃) a small amount will isomerize to the Z-form (≤0.2%). (For qualification purposes), store in a light-protected environment;

Quinoxaline ring: Avoid contact with strong oxidizing agents (such as potassium permanganate) to prevent ring opening of the heterocycle;

Hydrochloride salt: Stable under vacuum drying conditions, but will slowly dehydrochlorinate at high temperature and high humidity, releasing the free base.