4-(1-Piperazinyl)-1-methyl-1H-imidazo[4,5-c]pyridine dihydrochloride | CAS 186959-03-5 | 98% | White to Off-white Powder | Pharmaceutical Intermediate

1. Product Overview

4-(1-Piperazinyl)-1-methyl-1H-imidazo[4,5-c]pyridine dihydrochloride (CAS: 186959-03-5) is the dihydrochloride salt of an N-methylated imidazopyridine bearing a piperazin-1-yl substituent at the 4-position. The free base molecular formula is C₁₂H₁₇N₅ (MW 231.30 g/mol); the dihydrochloride salt formula is C₁₂H₁₉Cl₂N₅ with a molecular weight of 304.23 g/mol. This compound belongs to the imidazopyridine family—a privileged heterocyclic scaffold closely related to purines and benzodiazepines—and is structurally analogous to known serotonin (5-HT) receptor modulators and CNS-active agents. The dihydrochloride salt form provides excellent crystallinity, hygroscopic control, and high aqueous solubility, making it well-suited for biological assays, receptor-binding studies, and pharmaceutical R&D. The 1-methyl group on the imidazole nitrogen eliminates tautomerism and removes an H-bond donor, while the piperazine side chain enables salt formation and serves as a handle for further N-alkylation in SAR optimization.

2. Key Features and Advantages

• Imidazopyridine-Piperazine Hybrid: Combines the benzodiazepine-like imidazo[4,5-c]pyridine core (related to zolpidem, alpidem) with a 4-piperazinyl group, a classic motif in 5-HT₁A, 5-HT₂, and 5-HT₆ receptor ligands for anxiety, depression, and cognition enhancement.

• Dihydrochloride Salt Stability: Offers superior handling vs. free base—white to off-white crystalline powder, freely soluble in water and DMSO, enabling accurate dosing in buffer-based bioassays.

• N1-Methylation: Locks regiochemistry, improves membrane permeability (0 H-bond donors in free base; salt has protonated nitrogens), and reduces metabolic N-dealkylation risk.

• High Purity Grade: Typically supplied at ≥98% purity (HPLC), suitable for receptor-binding panels, in vivo studies, and lead optimization.

• CNS Drug Discovery Relevance: Closely related to clinical candidates targeting insomnia (GABAₐ modulators), schizophrenia (5-HT/D₂ dual ligands), and neurodegeneration (5-HT₆ antagonists).

• Scalable Availability: Available from 100 mg screening packs up to multi-gram quantities for pharmacological profiling and process development.

3. Main Applications

3.1 Pharmaceutical Intermediate & CNS Drug Discovery

This compound is a key building block and reference standard in neuropharmacology:

• Serotonin Receptor Ligands: The 4-(piperazin-1-yl)imidazo[4,5-c]pyridine scaffold is explored as 5-HT₁A agonists/partial agonists (anxiolytic/antidepressant), 5-HT₂A antagonists (antipsychotic), and 5-HT₆ modulators (cognitive enhancement in Alzheimer’s disease).

• GABAₐ-Benzodiazepine Site Modulators: Imidazo[4,5-c]pyridines are structural cousins of zolpidem and alpidem; this derivative with piperazine is investigated for subtype-selective sedative/hypnotic leads with reduced side-effect profiles.

• Dopamine-Serotonin Dual Ligands: The piperazine enables N-arylation/alkylation to build D₂/5-HT hybrid agents for schizophrenia and Parkinson’s-related psychosis.

3.2 Medicinal Chemistry & Library Synthesis

• The dihydrochloride can be basified to the free base for selective N-alkylation or acyl modification on the piperazine nitrogen (the less hindered secondary amine on piperazine is typically alkylated first).

• The imidazopyridine C2 and pyridine C6 positions (relative numbering) can be addressed via metalation or electrophilic substitution after protecting-group manipulation.

• Used to construct focused libraries around the 4-piperazinyl-imidazopyridine pharmacophore for GPCR screening (serotonin, dopamine, histamine H₁/H₃ panels).

3.3 Biological Assay & Probe Development

• Serves as a reference standard or tool compound in 5-HT receptor binding/displacement assays.

• Can be converted to radiolabeled (³H or ¹⁴C) or fluorescent probes via piperazine functionalization for receptor localization studies.

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 and moisture; hydrochloride salts can be hygroscopic and may deliquesce under high humidity. Use desiccant (silica gel) in the container.

• Keep away from strong bases (will liberate free base), strong oxidizers, and acidic vapors.

• For long-term storage (>6 months), store under desiccated conditions; after opening, reseal promptly and return to refrigerator. Avoid repeated freeze–thaw if made into aqueous stock solutions.

Handling Precautions

• Handle in a well-ventilated area or fume hood to avoid inhalation of fine powder.

• Avoid contact with skin, eyes, and clothing. Hydrochloride salts and piperazine derivatives can irritate mucous membranes.

• Use appropriate PPE as detailed in Section 6.

6. Safety Overview

Hazard Identification

• GHS Classification (typical supplier SDS): GHS07, Signal Word: Warning.

• Hazard Statements: H302 (Harmful if swallowed), H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation).

• Intended strictly for industrial and scientific research use; not for human or veterinary therapeutic use, not for food, feed, or cosmetic application.

• As a dihydrochloride salt of a basic amine/piperazine, it may cause eye/skin/respiratory irritation; prolonged or repeated exposure should be avoided.

First Aid Measures

• Inhalation: Move to fresh air. Seek medical attention if irritation or breathing difficulty persists.

• Skin Contact: Remove contaminated clothing. Rinse 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 mask or particulate respirator 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.

Disclaimer: This product is intended for industrial use and scientific research only. It is not for human or animal consumption, diagnostic, or therapeutic use. Users must ensure compliance with all applicable laws and regulations.