1. Product Overview
7-Methyl-4-(piperazin-1-yl)thieno[3,2-d]pyrimidine (CAS: 874781-16-5) is a fused bicyclic heterocyclic compound consisting of a thieno[3,2-d]pyrimidine core substituted with a methyl group at the 7-position and a piperazine moiety at the 4-position. The molecular formula is C₁₁H₁₄N₄S with a molecular weight of 234.32 g/mol. Also referenced as 1-(7-Methylthieno[3,2-d]pyrimidin-4-yl)piperazine, this compound belongs to the thienopyrimidine family, which is widely recognized as a privileged scaffold in medicinal chemistry due to its structural resemblance to purines and its ability to interact with diverse biological targets.
The presence of the basic piperazine side chain imparts favorable aqueous solubility and provides a handle for further derivatization or salt formation, while the thienopyrimidine core offers a rigid, planar aromatic system suitable for π–π stacking and hydrophobic interactions in protein binding pockets. It is predominantly used as a key intermediate and building block in the synthesis of kinase inhibitors, CNS-active agents, and other bioactive molecules targeting G-protein-coupled receptors (GPCRs) and enzymes.
2. Key Features and Advantages
• Privileged Heterocyclic Scaffold: Thieno[3,2-d]pyrimidine is a purine bioisostere with proven activity across multiple therapeutic areas, making this an excellent starting point for SAR studies.
• Piperazine Functionality: The 4-piperazinyl group enhances water solubility, enables salt formation, and serves as a site for further N-alkylation or acyl modification to fine-tune pharmacokinetics.
• High Purity Grade: Typically supplied at ≥98% purity (HPLC), meeting the rigor of pharmaceutical R&D and lead optimization campaigns.
• Balanced Lipophilicity: The 7-methyl group modulates log P and membrane permeability without excessively increasing molecular weight.
• Well-Characterized: Comprehensive analytical data (¹H/¹³C NMR, LC-MS, HPLC) are routinely provided with commercial batches.
• Scalable Supply: Available from 1 g laboratory packs up to multi-kilogram quantities for process development and pilot campaigns.
3. Main Applications
3.1 Pharmaceutical Intermediate & Drug Discovery
This compound is a central intermediate in the development of thienopyrimidine-based drug candidates. Typical applications include:
• Kinase Inhibitors: Thieno[3,2-d]pyrimidines are extensively explored as ATP-competitive kinase inhibitors targeting EGFR, VEGFR, CDK, and Aurora kinases for oncology indications.
• CNS Agents: The piperazine-substituted thienopyrimidine core appears in ligands for serotonin (5-HT₂A, 5-HT₆) and dopamine receptors, supporting antidepressant, antipsychotic, and nootropic drug discovery.
• Anticancer & Antiproliferative Agents: Used in constructing focused libraries aimed at apoptosis induction and cell-cycle arrest pathways.
• Anti-infectives: The scaffold is leveraged in designing antimicrobial and antiviral agents, including antifungal azole hybrids and antiviral protease inhibitors.
3.2 Medicinal Chemistry & Library Synthesis
The C4-piperazine can be readily alkylated or acylated, while the thienopyrimidine core tolerates electrophilic substitution at the 5- and 6-positions or metalation for cross-coupling. This makes 874781-16-5 a versatile building block for:
• Parallel synthesis of piperazine-derived analogues to optimize ADME and receptor selectivity.
• Structure–activity relationship (SAR) exploration around the thienopyrimidine pharmacophore.
• Design of fluorescent or radiolabeled probes when further functionalized with reporter groups.
3.3 Organic Synthesis
Beyond pharma, the compound serves as a model substrate in heterocyclic chemistry for studying nucleophilic aromatic substitution on thienopyrimidines (the 4-chloro precursor is displaced by piperazine to afford this product) and for developing new piperazine-aryl coupling methodologies.
4. Technical Specifications
5. Storage and Handling
Storage Conditions
• Store in a cool, dry place at 2–8 °C in a tightly sealed container.
• Protect from light; amber vials or foil wrapping are recommended.
• Keep away from strong acids, strong oxidizers, and moisture-sensitive environments.
• For long-term storage (>6 months), consider keeping under inert atmosphere (argon or nitrogen) to prevent slow oxidation of the piperazine nitrogen.
Handling Precautions
• Handle in a well-ventilated area or fume hood to avoid inhalation of fine dust.
• Avoid direct contact with skin, eyes, and clothing.
• Use appropriate PPE as detailed in Section 6.
6. Safety Overview
Hazard Identification
• Not classified as a GHS hazardous substance under standard regulations based on available data, but intended strictly for industrial and scientific research use.
• May cause mild irritation to eyes, skin, and respiratory tract upon contact or dust inhalation.
• The piperazine moiety can form aerosols or fine dust; prolonged or repeated exposure should be avoided.
• Not for human or veterinary therapeutic use, not for food or cosmetic application.
First Aid Measures
• Inhalation: Move to fresh air. Seek medical attention if coughing, wheezing, or irritation persists.
• Skin Contact: Remove contaminated clothing. Wash affected area thoroughly with soap and water.
• Eye Contact: Rinse immediately with plenty of running water for at least 15 minutes, holding eyelids open. Consult an ophthalmologist if irritation continues.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Seek immediate medical attention.
Personal Protective Equipment (PPE)
• Eye/Face Protection: Safety goggles or face shield.
• Hand Protection: Nitrile chemical-resistant gloves.
• Body Protection: Lab coat, long sleeves, closed-toe shoes.
• Respiratory Protection: NIOSH-approved dust respirator or particulate mask if handling generates airborne particles.
Disposal Considerations
• Dispose of as hazardous chemical waste per local, regional, and national regulations.
• Do not discard in drains or release into the environment.
• Incinerate in a licensed chemical waste facility.