2H-Imidazol-2-one, 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4,5,6,7-tetrahydro-4-methyl-2H-pyrazolo[4,3-c]pyridin-3-yl]-3-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-dihydro-

China [CN]

Core Application: A key intermediate in the final stage of FLT3/JAK kinase inhibitor API synthesis, directly used in subsequent steps such as heterocyclic modification and salt formation, for the preparation of innovative drug APIs for the treatment of hematological malignancies and autoimmune diseases.

Key Structural Features: 1. Tricyclic fused scaffold: pyrazolopyridine + imidazolinone (closed-ring form) + indazole, the core active nucleus of the drug, exhibiting extremely high target selectivity; 2. Retention of the **(4S) single chiral center and difluorinated aryl group**, with a structure highly similar to the final API; 3. No protecting groups, all functional groups are part of the drug scaffold, and the reaction site is only the active hydrogen on the heterocycle; 4. Fully reduced heterocycle (tetrahydropyrazolopyridine + dihydroimidazolinone), with significantly better chemical stability than the aromatic form.

Key Physicochemical Properties (Derived): 1. Appearance: White to off-white crystalline powder (typical form of the final intermediate, high crystallinity, good flowability); 2. Solubility: Slightly soluble in water, readily soluble in dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), soluble in tetrahydrofuran, dichloromethane, sparingly soluble in alcohols/petroleum ether (lipophilicity significantly increased after tricyclic fusion); 3. Stability: High stability, stable for more than 12 months under vacuum and light protection at room temperature, resistant to weak acids/bases, avoid strong oxidizing agents/high temperatures (≥100℃ may cause heterocyclic rearrangement); 4. Melting point: Expected 220~240℃ (tricyclic fusion + chiral center + multiple aryl groups, high melting point, can be used as an important indicator of purity).

Core Quality Indicators (ICH Compliant): 1. Chiral purity (ee value): ≥99.8% (core indicator for the final intermediate, chiral impurities ≤0.1%, directly affecting the efficacy of the final API); 2. Chemical purity (HPLC): ≥99.5% (normalization method); 3. Moisture content: ≤0.2% (Karl Fischer method, strict moisture control); 4. Key impurities: Uncyclized intermediate ≤0.1%, indazole defluorination impurity ≤0.05%, chiral isomer impurity ≤0.1%; 5. Residual solvents: Complies with ICH Q3C Class 1/2/3 limits (DMSO ≤0.1%, DMF ≤0.088%, dichloromethane ≤0.06%); 6. Residue on ignition: ≤0.1%