1-(Adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
[CAS# 1430845-70-7]

Identification

• Classification: Organic raw materials >> Organoboron compounds
• Name: 1-(Adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
• Synonyms: 1-(1-adamantylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole
• Molecular Formula: C₂₁H₃₃BN₂O₂
• Molecular Weight: 356.31
• CAS Registry Number: 1430845-70-7
• SMILES: B1(OC(C(O1)(C)C)(C)C)C2=C(N(N=C2)CC34CC5CC(C3)CC(C5)C4)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 472.6±33.0 ºC 760 mmHg (Calc.)^*
• Flash point: 239.6±25.4 ºC (Calc.)^*
• Index of refraction: 1.612 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovory and Applicatios

The chemical substance 1-(adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole is a specialized pyrazole derivative incorporating an adamantyl group and a boronic ester, widely utilized in organic synthesis, particularly in pharmaceutical and materials chemistry. Its discovery and applications are well-documented in the literature, stemming from advancements in heterocyclic chemistry and organoboron reagents.

The origins of this compound are linked to the development of pyrazole-based molecules and boronic esters, both of which gained prominence in the late 20th century. Pyrazoles, five-membered nitrogen-containing heterocycles, have been studied since the 19th century for their presence in pharmaceuticals and agrochemicals. The introduction of specific substituents, such as the adamantyl group—a rigid, lipophilic cage-like structure—became feasible with improved alkylation techniques in the 1960s and 1970s. The boronic ester moiety, specifically the 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl group (pinacol boronate), was popularized in the 1980s and 1990s through the work of chemists like Akira Suzuki, who developed palladium-catalyzed cross-coupling reactions. These reactions, notably the Suzuki-Miyaura coupling, established boronic esters as key intermediates for forming carbon-carbon bonds. The combination of these elements in 1-(adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole reflects the strategic design of molecules for synthetic versatility and biological activity.

Synthetically, the compound is prepared through a multi-step process. A typical route starts with 5-methyl-1H-pyrazole, which is alkylated at the N-1 position using 1-adamantylmethyl chloride or bromide under basic conditions to introduce the adamantan-1-ylmethyl group. The 4-position of the pyrazole is then functionalized with the boronic ester, often via a halogenated intermediate. For instance, the pyrazole can be brominated at the 4-position, followed by a palladium-catalyzed borylation with bis(pinacolato)diboron or pinacolborane. These steps leverage established heterocyclic and organometallic chemistry protocols, ensuring regioselectivity and high yields. The adamantyl group is typically introduced early to enhance solubility and steric protection, while the boronic ester is added later to maintain its reactivity.

The primary application of 1-(adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole is as a synthetic intermediate in pharmaceutical chemistry. The boronic ester group is a key handle for Suzuki-Miyaura cross-coupling reactions, enabling the attachment of aryl or alkenyl groups to the pyrazole core. This is critical for synthesizing drug candidates, such as kinase inhibitors or receptor modulators, where the pyrazole scaffold is a privileged structure due to its ability to engage in hydrogen bonding and π-interactions with biological targets. The adamantyl group enhances lipophilicity and metabolic stability, improving the pharmacokinetic properties of the resulting molecules. The methyl group at the 5-position fine-tunes steric and electronic effects, optimizing binding affinity.

In addition to pharmaceuticals, the compound is used in materials science for synthesizing functionalized polymers or ligands, where the boronic ester facilitates cross-coupling to build complex molecular architectures. In academic research, it serves as a model compound for studying cross-coupling mechanisms, pyrazole reactivity, and the steric effects of bulky substituents like adamantyl. Its synthesis has also contributed to the development of new borylation methods and catalysts.

The significance of 1-(adamantan-1-ylmethyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole lies in its role as a versatile building block that combines the synthetic utility of boronic esters with the biological relevance of pyrazoles. Its development reflects progress in heterocyclic functionalization and organoboron chemistry. By enabling the efficient synthesis of complex, biologically active molecules, it has become a critical tool in advancing pharmaceutical, materials, and chemical research.