1-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one
[CAS# 1708975-38-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Piperazine
• Name: 1-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one
• Molecular Formula: C₁₇H₂₆N₄O₃
• Molecular Weight: 334.41
• CAS Registry Number: 1708975-38-5
• SMILES: CN1CCN(C(=O)C1)CC2=C(N=C3C(=C2)CCCN3)C(OC)OC

Discovory and Applicatios

The chemical substance 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one is a complex heterocyclic compound, valued as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in the development of naphthyridine and piperazine derivatives, as well as acetal chemistry.

The origins of this compound are linked to the study of 1,8-naphthyridines, bicyclic heterocycles containing two nitrogen atoms, which have been explored since the early 20th century for their pharmacological properties. The tetrahydro-1,8-naphthyridine core, formed by partial reduction of the aromatic system, gained attention in the mid-20th century for its presence in bioactive molecules. The dimethoxymethyl group, an acetal, emerged as a protecting group for aldehydes in the 1960s, valued for its stability and ease of deprotection. Piperazin-2-one, a lactam derivative of piperazine, became a common scaffold in medicinal chemistry during the 1970s and 1980s due to its ability to enhance solubility and binding affinity. The specific combination of these elements—tetrahydro-1,8-naphthyridine with a dimethoxymethyl group, linked to a methylpiperazin-2-one via a methylene bridge—developed in the late 20th century to meet the pharmaceutical industry’s need for multifunctional intermediates with optimized pharmacokinetic profiles.

Synthetically, 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one is prepared through a multi-step process. A typical route starts with 1,8-naphthyridine, which is selectively reduced to 5,6,7,8-tetrahydro-1,8-naphthyridine using catalytic hydrogenation. The 2-position is functionalized with a dimethoxymethyl group by formylation followed by acetal formation with methanol under acidic conditions. The 3-position is equipped with a methylene linker, often via a chloromethyl intermediate formed through electrophilic substitution, which is then reacted with 4-methylpiperazin-2-one under basic conditions to form the carbon-nitrogen bond. The piperazin-2-one is typically pre-methylated at the 4-position using methyl iodide or a similar reagent. These steps rely on well-established heterocyclic, acetal, and alkylation chemistry, ensuring regioselectivity and high yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The tetrahydro-1,8-naphthyridine core is a privileged scaffold in drugs targeting cancer, inflammation, and neurological disorders, due to its ability to engage in π-interactions and hydrogen bonding. The dimethoxymethyl group protects a latent aldehyde, which can be deprotected to enable further transformations, such as reductive amination or Wittig reactions. The 4-methylpiperazin-2-one moiety enhances solubility and provides a lactam for additional functionalization, such as amide formation. This compound is used in the synthesis of kinase inhibitors, receptor antagonists, and other therapeutic agents, where the combination of polar and hydrophobic groups optimizes pharmacokinetic properties and target affinity.

In academic research, the compound is employed to study naphthyridine reactivity, acetal chemistry, and the effects of piperazine-based substituents on biological activity. Its synthesis has contributed to the development of selective reduction and alkylation methods. The compound also finds use in the synthesis of specialty chemicals, such as molecular probes, where the heterocyclic core and polar functionalities are advantageous.

The significance of 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one lies in its role as a multifunctional intermediate that combines the biological relevance of tetrahydro-1,8-naphthyridine with the synthetic versatility of acetals and piperazin-2-one. Its development reflects progress in heterocyclic synthesis, protecting group strategies, and regioselective functionalization. By enabling the efficient synthesis of complex, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.