3-Chloro-4-(2-pyridylmethoxy)aniline
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Product Description
3-Chloro-4-(2-pyridylmethoxy)aniline is an aniline derivative with a benzene ring at its core, bearing an amino group (−NH₂) at position 1. At position 3, there's a chlorine atom (−Cl), and at position 4, a methoxy group is attached to a 2-pyridyl group through an oxygen atom, forming an ether linkage. Due to its aniline group, pyridine ring, and ether linkage, it is likely soluble in organic solvents like ethanol, DMSO, and DMF, but less so in water. 3-Chloro-4-(2-pyridylmethoxy)aniline is primarily used as a pharmaceutical intermediate, particularly in the synthesis of anticancer drugs and H₂ receptor antagonists like Famotidine.
Note: 3-Chloro-4-(2-pyridylmethoxy)aniline produced by our company is a chemical raw material and is only used for scientific research and production. It cannot be used directly as a drug.
Synthesis Methods
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Synthesis Route 1:
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Step 1: Condensation of 3-chloro-4-(2-pyridylmethoxy)aniline (I) with ethyl cyanoacetate (II) at 100-115°C to give the N-aryl 2-cyanoacetamide (III).
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Step 2: Reduction of 3-ethoxy-4-phthalimido-1-nitrobenzene (IV) with H₂ over Pd/C in THF at 50°C, followed by coupling of the resulting aniline with the cyano amide (III) using triethyl orthoformate in refluxing propanol to afford the 3-amino-2-cyanopropenamide derivative (V).
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Step 3: Intramolecular cyclization of propenamide (V) using POCl₃ in acetonitrile at 60-70°C to obtain the 6-phthalimidoquinoline derivative, which is then hydrolyzed using NH₄OH in EtOH at 62-68°C to give the 6-aminoquinoline (VI).
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Step 4: Acylation of compound (VI) with 4-(dimethylamino)-2-butenoyl chloride (IX) in the presence of NMP to obtain the final product.
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Synthesis Route 2:
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Step 1: Reduction of 4-chloro-7-ethoxy-6-nitroquinoline-3-carbonitrile (XI) to the corresponding amine (XII) using Fe and acetic acid in refluxing methanol.
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Step 2: Acylation of (XII) with 4-(dimethylamino)-2-butenoyl chloride (IX) in the presence of NMP in acetonitrile or DMF to yield carboxamide (XIII).
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Step 3: Coupling of (XIII) with 3-chloro-4-(2-pyridylmethoxy)aniline (I) using pyridinium chloride in refluxing isopropanol or 2-methoxyethanol.
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Uses
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Pharmaceutical Intermediate: Primarily used in the synthesis of key side chain components of the anticancer drug neratinib.
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Research Chemical: Used in academic and industrial research, particularly in the fields of medicinal chemistry and drug discovery.
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Other Applications: Potential use in agrochemicals or as an intermediate in the synthesis of dyes due to its functional groups that provide sites for further chemical modification and biological activity.
Properties
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Molecular Formula: C₁₂H₁₁ClN₂O
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Molecular Weight: 234.68 g/mol
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Physical Appearance: White to pale yellow powder
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Melting Point: 91.0-95.0°C
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Boiling Point: Approximately 402.5°C (estimated)
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Density: 1.292 g/cm³ (estimated)
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Solubility: Limited solubility in water; soluble in organic solvents like ethanol, DMSO, and DMF.
Structural Features
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Core Structure: Aniline (–NH₂ substituted benzene)
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Substituents:
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Chloro group at the 3-position
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(2-pyridyl)methoxy group at the 4-position
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Functional Groups:
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Primary aromatic amine (–NH₂ on benzene)
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Ether linkage (–O–CH₂–pyridyl)
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Aromatic heterocycle (pyridine ring)
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Aryl chloride (–Cl substituent)
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Chemical Safety and Handling
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Hazards:
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Skin irritation (H315)
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Eye irritation (H319)
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Respiratory irritation (H335)
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Protective Measures:
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Wear protective gloves, eye protection, and a mask (P280)
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Wash with soap and water in case of skin contact (P302 + P352)
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Rinse eyes with clean water in case of eye contact (P305 + P351 + P338)
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Storage Conditions: Store in a dry, inert atmosphere at room temperature, away from light.
Regulatory Information
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REACH Compliance: Not listed on various regulatory inventories such as TSCA, AICS, DSL, ENCS, ISHL, KECI, PICCS, IECSC, and NZIoC.
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WGK Germany: Water hazard class 3 (highly hazardous to water).
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Transport Information: Not regulated as a dangerous good under ADR, IMDG, or IATA regulations.