6-Chloro-4-(ethylamino)-3-pyridinecarboxaldehyde
[CAS# 959163-01-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Chloropyridine
• Name: 6-Chloro-4-(ethylamino)-3-pyridinecarboxaldehyde
• Molecular Formula: C₈H₉ClN₂O
• Molecular Weight: 184.62
• CAS Registry Number: 959163-01-0
• SMILES: CCNC1=CC(=NC=C1C=O)Cl

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 347.4±42.0 ºC 760 mmHg (Calc.)^*
• Flash point: 163.9±27.9 ºC (Calc.)^*
• Index of refraction: 1.624 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P305+351+338-P302+352

Discovory and Applicatios

6-Chloro-4-(ethylamino)-3-pyridinecarboxaldehyde is a heteroaromatic compound that features a substituted pyridine ring bearing three functional groups: a chlorine atom at the 6-position, an ethylamino group at the 4-position, and a formyl group (–CHO) at the 3-position. Its molecular formula is C₈H₉ClN₂O. The combination of these substituents contributes to its chemical reactivity and its value as an intermediate in organic synthesis.

The compound is commonly synthesized through sequential substitution and functionalization of pyridine derivatives. One typical approach involves the electrophilic chlorination of a suitable pyridine precursor, followed by nucleophilic substitution to introduce the ethylamino group, and a directed formylation reaction to introduce the aldehyde functionality at the desired ring position. Such syntheses rely on regioselective transformations that are well-documented in the literature for functionalizing the pyridine ring.

6-Chloro-4-(ethylamino)-3-pyridinecarboxaldehyde is mainly used as a building block in medicinal chemistry. Its functional groups enable a wide range of chemical modifications. The aldehyde moiety is reactive toward nucleophiles and is commonly employed in the formation of Schiff bases, imines, and heterocyclic compounds. The ethylamino group contributes both basicity and hydrogen bonding potential, making it a useful substituent for interacting with biological targets. The chlorine atom at the 6-position provides a convenient handle for cross-coupling reactions, such as Suzuki or Buchwald-Hartwig couplings, allowing for the installation of various aryl or heteroaryl groups.

In drug discovery, derivatives of this compound have been investigated for their potential biological activities, including kinase inhibition and central nervous system targeting. The pyridine ring is a common structural motif in pharmaceuticals due to its aromatic stability and ability to participate in π-stacking and coordination with metal ions or active site residues in proteins. While 6-chloro-4-(ethylamino)-3-pyridinecarboxaldehyde itself is not a marketed drug, it serves as a key intermediate in the synthesis of lead compounds evaluated for therapeutic use.

The combination of an electron-withdrawing aldehyde and an electron-donating amino group on the same aromatic ring can modulate the electronic distribution across the molecule. This affects both its reactivity in chemical synthesis and its potential interaction profile in biological systems. The structural features of this molecule make it particularly useful for constructing small molecule libraries where control over electronic and steric factors is important.

From a physical and chemical perspective, the compound is typically a pale solid or light-colored crystalline material. It is soluble in organic solvents such as methanol, dimethyl sulfoxide, and dichloromethane. Its stability is adequate under standard laboratory conditions, although the aldehyde group can be sensitive to oxidation or condensation reactions if not stored properly. It is recommended to store it in airtight containers under an inert atmosphere or in a refrigerator to prolong shelf life.

Handling of 6-chloro-4-(ethylamino)-3-pyridinecarboxaldehyde requires standard laboratory safety practices. The compound should be manipulated in a well-ventilated fume hood with appropriate personal protective equipment. As with many aldehydes and halogenated amines, exposure should be minimized due to potential irritant or sensitizing effects.

Overall, 6-chloro-4-(ethylamino)-3-pyridinecarboxaldehyde is a synthetically versatile intermediate widely applied in the design and development of complex organic molecules, particularly in pharmaceutical research. Its reactive sites enable diverse derivatizations, making it an essential tool in constructing functionalized heterocyclic compounds.

References

2020. Ripretinib. Pharmaceutical Substances, 1.
URL: https://www.thieme.de/en/thieme-chemistry/pharmaceutical-substances-54712.htm