6-Chloro-4-methoxypyridine-3-carbaldehyde 1256823-05-8 97% off-white to light yellow crystalline powder pharmaceutical intermediate

1. Product Overview

6-Chloro-4-methoxypyridine-3-carbaldehyde (CAS 1256823-05-8), also referred to as 6-chloro-4-methoxynicotinaldehyde or 6-chloro-4-methoxypyridine-3-carboxaldehyde, is a substituted pyridine aldehyde featuring a chlorine at the 6-position, a methoxy at the 4-position, and a reactive aldehyde group at the 3-position of the pyridine ring. It serves as a versatile electrophilic and nucleophilic building block in medicinal chemistry and heterocyclic synthesis. The compound typically appears as an off-white to light yellow crystalline powder, widely used for constructing pyridine-based active pharmaceutical ingredients (APIs), kinase inhibitors, and CNS or anti-infective agents via aldehyde condensation, reductive amination, and cross-coupling at the aryl chloride.

2. Key Features and Advantages

• Reactive aldehyde enables condensation with amines/hydrazines (Schiff bases, imines), reductive amination, and oxidation to carboxylic acid or reduction to benzyl alcohol for ether/ester formation.

• 6-Chloro is a labile aryl halide supporting Suzuki, Sonogashira, and Buchwald–Hartwig cross-couplings for late-stage diversification of the pyridine core.

• 4-Methoxy group stabilizes the pyridine ring and can be demethylated to phenol under strong Lewis acid conditions for additional O-functionalization.

• Pyridine scaffold is a privileged heterocycle in drug discovery (kinase inhibitors, antivirals, CNS agents), enabling rapid SAR exploration via orthogonal C3-aldehyde and C6-Cl reactivity.

• High purity grade (≥97%) with well-established analytical profile (NMR, HPLC, LC-MS) for QC release in pharmaceutical R&D and custom synthesis.

3. Main Applications

• Pharmaceutical intermediate for pyridine-based drug candidates, especially kinase inhibitors, antiviral and CNS programs where 3-aldehyde-4-methoxy-6-chloropyridine is a key pharmacophore.

• Building block for pyrido-fused heterocycles (pyrido[2,3-d]pyrimidines, quinazolines) via aldehyde condensation with amidines/guanidines and subsequent cross-coupling at C6.

• Intermediate in CRO/CDMO custom synthesis and academic research for heterocyclic library generation, reductive amination screens, and multicomponent reactions (e.g., Hantzsch-type pyridine formations).

• Precursor to 6-chloro-4-methoxypyridine-3-methanol (via NaBH₄ reduction) and 6-chloro-4-methoxynicotinic acid (via aldehyde oxidation), relevant to agrochemical and dye chemistry.

• Used in fragment-based drug design to introduce an aldehyde handle on the 3-position of a 4-methoxy-6-chloropyridine for imine/amide linkage to aromatic or aliphatic fragments.

4. Technical Specifications

5. Storage and Handling

Store in a cool, dry place at 2–8 °C in a tightly sealed, light-protected container under an inert atmosphere (nitrogen or argon) to prevent oxidation of the aldehyde group and moisture uptake. For long-term storage, keep at –20 °C in desiccated conditions. The aldehyde is sensitive to air oxidation (to carboxylic acid) and can undergo aldol-type condensation under basic conditions; avoid contact with strong bases, nucleophiles, or prolonged exposure to humid air. Handle in a well-ventilated area with standard PPE (lab coat, nitrile gloves, safety glasses). Reseal promptly after use. Under recommended conditions, shelf life is typically 12–24 months; periodic HPLC check advised due to aldehyde lability.

6. Safety Overview

Intended for research and synthetic use only; not for direct human or veterinary therapeutic administration. May cause irritation to eyes, skin, and respiratory tract upon contact or dust inhalation (GHS07: H315–H319–H335). Aldehydes and chlorinated pyridines can be mildly irritating to mucous membranes and may cause sensitization; handle as a reactive aromatic aldehyde with standard laboratory precautions. Prevent dust/vapor generation. In case of skin contact, wash thoroughly with soap and water; for eye contact, rinse cautiously with plenty of water for several minutes and seek medical advice if irritation persists. Avoid contact with strong oxidizers and amines unless intentionally performing a reaction. Dispose according to local regulations for halogenated heterocyclic aldehydes. Always consult the latest SDS from the supplier before use.