N1-[2-(Dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-1,2,4-benzenetriamine
[CAS# 1421372-66-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound
• Name: N1-[2-(Dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-1,2,4-benzenetriamine
• Synonyms: Mutated EGFR-IN-1
• Molecular Formula: C₂₅H₃₁N₇O
• Molecular Weight: 445.56
• CAS Registry Number: 1421372-66-8
• SMILES: CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)N)N(C)CCN(C)C)OC

Properties

• Solubility: Insoluble (3.5E^-4 g/L) (25 °C), Calc.^*, DMSO 12 mg/mL (Expl.)
• Density: 1.21±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 676.5±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 363.0±34.3 °C (Calc.)^*
• Index of refraction: 1.635 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2015 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

N1-[2-(Dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-1,2,4-benzenetriamine is a complex organic compound featuring multiple functional groups commonly found in biologically active molecules. Structurally, it consists of a benzenetriamine core substituted with a methoxy group at position 5 and two distinct N-substituents: a dimethylaminoethyl-methylamine side chain and a pyrimidinyl-indole moiety. The compound exhibits several pharmacophoric features such as aromatic rings, a basic dimethylamino group, and heterocyclic systems, which contribute to its interaction with biological targets.

This compound appears to have originated from medicinal chemistry programs aimed at designing small-molecule modulators of signaling pathways, especially those involving protein kinases, G protein-coupled receptors (GPCRs), or other cellular regulators. The pyrimidine ring is a well-known scaffold in drug discovery, as it mimics adenine and can interact with ATP-binding sites of kinases. The 1-methyl-1H-indol-3-yl unit is also common in ligands for serotonin receptors and other CNS targets. Additionally, the presence of a 5-methoxy substitution on the aromatic ring can increase lipophilicity and affect the electronic character of the molecule, influencing its binding and metabolic stability.

Although public literature on this specific compound is limited, similar structures are often explored in the development of anticancer agents, anti-inflammatory drugs, or CNS-active compounds. The combination of polar and nonpolar regions in the molecule supports cell membrane permeability while maintaining aqueous solubility, desirable traits for oral bioavailability. Its amine groups suggest possible salt formation for formulation and improved pharmacokinetics.

The synthesis of such a molecule typically involves multistep organic reactions, beginning with the functionalization of an aromatic diamine, selective protection and substitution reactions, and coupling steps to introduce the pyrimidinyl and indole units. Advanced protecting-group strategies and palladium-catalyzed cross-couplings, such as Buchwald–Hartwig amination or Suzuki reactions, may be employed. The final steps often include methylation or dimethylaminopropylation using methylating agents or alkyl halides under basic conditions.

In pharmaceutical development, molecules like N1-[2-(dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-1,2,4-benzenetriamine would undergo evaluation for receptor binding, enzymatic inhibition, cellular activity, and pharmacological profiles. If any activity is confirmed, additional analogues might be synthesized to study structure–activity relationships (SAR) and optimize potency, selectivity, metabolic stability, and toxicity.

Depending on its bioactivity, the compound might be formulated for various routes of administration. If targeting CNS receptors, formulation considerations must address blood–brain barrier permeability. If acting on peripheral targets, optimizing for plasma half-life and minimizing off-target activity becomes critical. Analytical techniques such as NMR, LC-MS, and HPLC would be essential to confirm purity and identity throughout development.

Given the structure, this compound likely falls within the scope of rational drug design aimed at multi-target modulation or selective inhibition of specific signaling pathways. While the specific pharmacological application of this compound remains unclear from available public sources, its design aligns with trends in the development of kinase inhibitors, receptor antagonists, or small-molecule probes for cellular pathways relevant in oncology, immunology, or neurology.

References

2016. Osimertinib. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com

2019. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular Pharmacology, 96(5).
DOI: 10.1124/mol.119.115964

2020. Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. Proceedings of the National Academy of Sciences, 117(47).
DOI: 10.1073/pnas.2005463117