5, 5'-[(2R, 5R)-1-[3,5-difluoro-4-(4-(4-fluorophenyl)- 1-piperidinyl)phenyl]-2,5-pyrrolidinediyl]bis[6-fluoro-2-(2S)-2-pyrrolidinyl 1H-benzimidzole]

China [CN]

Melting point: 235~240℃ (decomposition), melting is accompanied by Boc protecting group removal, benzimidazole ring opening, and molecular chain cleavage, therefore it cannot be used for purity/chirality determination, only as a reference indicator of thermal stability;

Specific rotation: [α]D25​=−95° −102° (c=0.2, DMSO), the sole indicator for determining the complete chiral configuration; a deviation of ±2° from the optical rotation value indicates chiral racemization/excessive impurities, requiring immediate disposal;

Solubility: Very slightly soluble in water (solubility <0.005g/L at 25℃, strongly hydrophobic), readily soluble in pure DMSO and DMF, slightly soluble in N-methylpyrrolidone (NMP), very slightly soluble in methanol/ethanol/tetrahydrofuran, insoluble in conventional solvents such as ethyl acetate, dichloromethane, and n-hexane (only strongly polar aprotic solvents can dissolve it, suitable for subsequent macrocyclization processes);

Dissociation constant: pKa≈5.8 (benzimidazole N-H), pKa≈10.5 (Boc carbamate N-H), pKa≈14.2 (pyrrolidine ring imine), weakly alkaline in aqueous solution (pH 7.5~8.0), solubility does not significantly improve after salt formation with strong acids (dominated by the ultra-large molecular structure);

Stability:

Storage conditions: Vacuum sealed + inert gas (N₂) filling, 2~8℃ in a cool, dark place (mandatory requirement), shelf life ≥24 months; storage at room temperature (25℃) for ≤3 days, prolonged storage at room temperature will cause Boc group removal and slight opening of the benzimidazole ring;

Acid-base stability: Stable under neutral/weakly alkaline conditions (pH 7~10), **under strongly acidic conditions (TFA/HCl, pH<2)**, the Boc protecting group can be quantitatively removed at room temperature (without other functional group side reactions); strong bases (pH>12) will cause racemization of the pyrrolidine chiral center + The benzimidazole ring opens, leading to immediate failure;

Chiral stability: Under conditions of 2-8℃, N₂ protection, avoidance of light, and absence of metal catalysts, no racemization occurs at any of the 8 chiral centers;