1. Product Overview
CAS 1275595-86-2 is a key chiral intermediate in the synthesis of Pibrentasvir (ABT-530), a potent second-generation hepatitis C virus (HCV) NS5A inhibitor used in combination therapy (Mavyret®/Maviret®) for the treatment of chronic HCV infection. This intermediate features a highly functionalized structure containing a dimethylphenyl group, a valine-derived chiral center, a fluorophenyl moiety, and a proline-like pyrrolidine-2-carboxylic acid core. The (2S,3S) stereochemistry is critical for maintaining the conformational integrity required for NS5A target binding affinity and ultimately the clinical efficacy of the final API.
2. Key Features and Benefits
• Critical Chiral Intermediate: The (2S,3S) stereochemistry is essential for the biological activity of Pibrentasvir; high enantiomeric purity (≥99% ee) ensures reproducible API quality and regulatory compliance.
• Multi-Functional Architecture: Incorporates aromatic (dimethylphenyl, fluorophenyl), heterocyclic (pyrrolidine), and amino acid (valine-derived) pharmacophores, providing diverse handles for further elaboration in API synthesis.
• Proven Clinical Relevance: Pibrentasvir, the parent drug of this intermediate, is approved globally (FDA, EMA, PMDA) for all major HCV genotypes (1–6) with >90% cure rates in 8-week regimens.
• High Purity & Batch Consistency: Supplied at ≥95% or ≥98% (HPLC), with full Certificate of Analysis (CoA) including ¹H NMR, chiral HPLC, and residual solvent analysis for each lot.
• Regulatory-Ready: Suitable for use in GMP-compliant API manufacturing; impurity profile and residual metal content meet ICH Q3A/Q3B guidelines.
3. Major Applications
• Pibrentasvir (ABT-530) API Synthesis: The primary and most critical application—this intermediate is coupled, deprotected, and further functionalized through 3–5 additional steps to produce the final NS5A inhibitor API.
• HCV NS5A Inhibitor SAR Studies: Used in medicinal chemistry programs to explore structural variants of Pibrentasvir, including analogs with modified valine, proline, or aromatic substituents for next-generation HCV therapies.
• Process Chemistry & Scale-Up: Employed in route scouting, process optimization, and tech transfer for commercial-scale Pibrentasvir manufacturing (kilogram to ton scale).
• Regulatory Filing Support: Provides essential data for DMF (Drug Master File), CMC (Chemistry, Manufacturing, and Controls) sections of NDA/MAA submissions, including impurity characterization and forced degradation studies.
• Analytical Method Development: Serves as a reference standard for HPLC, LC-MS, and chiral chromatography method development in Pibrentasvir quality control.
• Related Compound Library: Used to synthesize Pibrentasvir-related impurities and degradation products for analytical method validation and stability testing.
4. Technical Specifications
Item Description
Product Name Pibrentasvir Intermediate (Chiral Pyrrolidine Derivative)
Synonyms (2S,3S)-1-[(2S)-2-[[(2S)-2-[(1R)-1-[(2S)-2-[(2,2-dimethyl-1,3-dioxolan-4-yl)carbonyl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-2-fluorophenyl ester (simplified: Pibrentasvir Key Intermediate); ABT-530 Intermediate
CAS Number 1275595-86-2
Molecular Formula C₃₈H₄₆FN₃O₇ (representative; exact formula batch-specific)
Molecular Weight ~691.8 g/mol (representative)
MDL Number —
Assay (Purity) ≥95% / ≥98% (HPLC)
Enantiomeric Purity ≥99% ee (2S,3S)
Appearance White to off-white crystalline solid or powder
Melting Point Not reported (typical for complex peptide-like intermediates: 100–180 °C, batch-dependent)
Boiling Point ~950 °C (Predicted, high MW)
Density ~1.15–1.25 g/cm³ (Predicted)
pKa (Predicted) ~3.5 ± 0.3 (Carboxylic acid/ester), ~9.5 ± 0.5 (Amine/amide NH)
Calculated LogP ~4.0–5.5 (highly lipophilic due to aromatic + alkyl groups)
Polar Surface Area (PSA) ~120–150 Ų (estimated)
Hydrogen Bond Donors 2–3
Hydrogen Bond Acceptors 7–8
Rotatable Bonds 10–12
Solubility Soluble: DMSO (>50 mg/mL, sonication recommended), DMF, Methanol (slightly), Ethanol (slightly), DCM, Chloroform, THF, Acetone.
Practically Insoluble:Water (high LogP; may be converted to salt for aqueous work).
Spectral Data ¹H NMR (DMSO‑d₆, 400 MHz, representative): δ 0.85–1.35 (m, 18H, 4×CH₃ + dioxolane CH), 1.55–2.85 (m, 10H, pyrrolidine-CH₂ + valine CH/CH₂), 3.80–4.50 (m, 4H, CH-O + CH-N), 6.80–7.60 (m, 8H, aromatic H), 8.20 (d, J≈8.0 Hz, 1H, NH), 8.50 (d, J≈8.0 Hz, 1H, NH), 10.5 (br s, 1H, COOH/NH).
¹³C NMR (DMSO‑d₆):δ 18–28 (CH₃), 35–65 (aliphatic Cs), 72.0 (dioxolane C), 110–165 (aromatic + heteroaromatic Cs), 165.0 (C=O, ester), 170.0 (C=O, amide), 172.0 (C=O, acid).
SMILES Complex (see full structure in CoA)
InChI Key Batch-specific (available upon request)
Storage (Powder) -20°C, sealed, protected from light & moisture; stable ≥18–24 months
Sensitivity Moisture-sensitive (ester groups); protect from strong acid/base
HS Code 2933.99.90 / 2941.90.90
5. Storage and Handling
• Storage: Store in a tightly sealed container at -20°C (or 2–8°C for short-term), protected from light and moisture. For long-term storage (>12 months), keep in a desiccator under an inert atmosphere (N₂ or Ar). Stable for at least 18–24 months from date of manufacture.
• Handling: Allow vial to reach room temperature before opening to prevent moisture condensation. Dissolve in anhydrous DMSO, DMF, DCM, or MeOH as required. Minimize exposure to protic solvents to prevent ester hydrolysis.
• Ester Stability: The fluorophenyl ester and dioxolane-protected carboxyl groups are sensitive to hydrolysis under acidic or basic conditions. Use anhydrous solvents and neutral pH conditions for coupling reactions.
• Solution Preparation: Prepare stock solutions in anhydrous DMSO (10–50 mM). The compound may require gentle warming (≤50°C) and sonication for complete dissolution. Protect from light.
• Solution Stability: DMSO stocks are stable at -20°C for 1–3 months. Avoid repeated freeze-thaw cycles; aliquot upon preparation.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (structural alert—handle with caution).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P261: Avoid breathing dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P313: IF exposed: Get medical advice/attention.
• P330: Rinse mouth if swallowed.
• P337+P313: If eye irritation persists: Get medical advice/attention.
• P403+P233: Store in a well-ventilated place. Keep container tightly closed.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce irritating/acrid smoke (HF, CO, NOₓ). Hydrogen fluoride is extremely toxic and corrosive.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood. Keep container closed when not in use. Store at -20°C (or 2–8°C short-term), protected from light and moisture. Keep away from strong oxidizers, strong acids/bases, and heat sources.
• Hazardous Decomposition Products: Hydrogen fluoride (HF), nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially bioactive and genotoxic compound (structural alert present).
