2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester
[CAS# 940284-98-0]

Identification

• Classification: Organic raw materials >> Organoboron compounds
• Name: 2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester
• Synonyms: 2-(4-Boc-piperazino)pyrimidine-5-boronic acid pinacol ester
• Molecular Formula: C₁₉H₃₁BN₄O₄
• Molecular Weight: 390.28
• CAS Registry Number: 940284-98-0
• SMILES: B1(OC(C(O1)(C)C)(C)C)C2=CN=C(N=C2)N3CCN(CC3)C(=O)OC(C)(C)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 525.2±60.0 ºC 760 mmHg (Calc.)^*
• Flash point: 271.4±32.9 ºC (Calc.)^*
• Index of refraction: 1.537 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H301-H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovory and Applicatios

2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester is a heterocyclic organoboron compound combining a pyrimidine ring, a piperazine moiety protected with a tert-butoxycarbonyl (Boc) group, and a boronic acid pinacol ester. The molecule integrates multiple functional groups that enable selective transformations in organic synthesis. Boronic acid esters, such as the pinacol derivative, are widely used in cross-coupling reactions, including Suzuki–Miyaura couplings, to form carbon–carbon bonds. The pyrimidine ring serves as an electron-deficient heteroaromatic scaffold, while the Boc-protected piperazine provides a masked nucleophilic site that can be deprotected under mild acidic conditions for further derivatization.

The compound is typically synthesized via functionalization of a halogenated pyrimidine precursor, often a 5-bromo- or 5-chloropyrimidine, which is coupled with a boronate ester under palladium-catalyzed conditions to introduce the boronic acid functionality. The N-Boc piperazine can be installed either prior to or after boronation, depending on the desired chemoselectivity. Reaction conditions are optimized to prevent hydrolysis of the boronate ester and to maintain protection of the piperazine nitrogen. The product is generally isolated as a crystalline solid or an oil and can be purified by column chromatography.

In synthetic organic chemistry, 2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester serves as a versatile intermediate for constructing functionalized pyrimidine derivatives. The boronic ester group enables Suzuki–Miyaura coupling to introduce various aryl or heteroaryl groups at the 5-position of the pyrimidine ring. The Boc-protected piperazine allows for selective deprotection and subsequent modification, such as acylation, sulfonylation, or alkylation, to generate a diverse array of substituted piperazine derivatives. These features make it a valuable building block for medicinal chemistry, where substitution patterns on the pyrimidine and piperazine rings influence biological activity and pharmacokinetic properties.

In drug discovery, derivatives prepared from this intermediate have been explored for potential activity as kinase inhibitors, receptor ligands, and other bioactive heterocyclic compounds. The combination of a heteroaromatic scaffold with a piperazine substituent is common in pharmaceuticals due to its ability to interact with protein targets via hydrogen bonding, pi-stacking, and electrostatic interactions. The boronic ester allows modular introduction of structural diversity, supporting rapid generation of compound libraries for structure–activity relationship studies.

The compound is also relevant in methodology research. Its boronate ester can serve as a model substrate to study reaction conditions, catalyst performance, and selectivity in cross-coupling chemistry. Researchers utilize such molecules to optimize reaction parameters, investigate solvent and temperature effects, and evaluate protective group strategies for nitrogen-containing heterocycles. The N-Boc group provides stability during these transformations, enabling efficient synthesis of complex derivatives.

Physically, 2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester is stable under standard laboratory conditions, with solubility in polar organic solvents such as dimethylformamide, dichloromethane, and tetrahydrofuran. The boronic ester should be protected from moisture and strong acids to prevent hydrolysis, while the Boc group remains stable under neutral and mildly basic conditions. The combination of reactivity, stability, and protective group functionality makes it suitable for multistep synthetic sequences.

Overall, 2-[4-(N-Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester is a multifunctional heterocyclic intermediate widely used in organic synthesis. Its boronic ester and Boc-protected piperazine allow selective chemical transformations, enabling the construction of complex pyrimidine derivatives and bioactive molecules for pharmaceutical research and method development.

References

2022. Tropomyosin receptor kinase (trk) degradation compounds and methods of use. WO Patent, 2022218289.

2022. Mk2 degraders and uses thereof. WO Patent, 2023278759.