[(3R)-1-[7-(2-Butynyl)-2,3,6,7-tetrahydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-2,6-dioxo-1H-purin-8-yl]-3-piperidinyl]carbamic acid 1,1-dimethylethyl ester
[CAS 668273-75-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: [(3R)-1-[7-(2-Butynyl)-2,3,6,7-tetrahydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-2,6-dioxo-1H-purin-8-yl]-3-piperidinyl]carbamic acid 1,1-dimethylethyl ester
• Synonyms: tert-butyl N-[(3R)-1-[7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-2,6-dioxopurin-8-yl]piperidin-3-yl]carbamate
• Molecular Formula: C₃₀H₃₆N₈O₄
• Molecular Weight: 572.66
• CAS Registry Number: 668273-75-4
• SMILES: CC#CCN1C2=C(N=C1N3CCC[C@H](C3)NC(=O)OC(C)(C)C)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C

Properties

• Solubility: Insoluble (1.7E^-4 g/L) (25 °C), Calc.^*
• Density: 1.32±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of refraction: 1.659 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Risk Statements: H300-H315-H319-H361-H372
• Safety Statements: P201-P202-P260-P264-P270-P280-P302+P352-P305+P351+P338-P308+P313-P310-P330-P332+P313-P362-P405-P501
• Transport Information: UN 2811

Discovery and Applications

[(3R)-1-[7-(2-butynyl)-2,3,6,7-tetrahydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-2,6-dioxo-1H-purin-8-yl]-3-piperidinyl]carbamic acid 1,1-dimethylethyl ester is a highly complex, stereochemically defined heterocyclic compound featuring multiple fused nitrogen-rich ring systems, a piperidine-linked carbamate protecting group, and several alkyl and aromatic substituents. The structure is notable for combining purine, quinazoline, and piperidine-derived frameworks into a single densely functionalized scaffold.

The central core of the molecule is a substituted purine derivative. Purines are bicyclic heteroaromatic systems composed of a fused imidazole and pyrimidine ring. In this compound, the purine framework is further functionalized at multiple positions, including carbonyl groups at the 2- and 6-positions, forming a 2,6-dioxopurine system. These carbonyl groups contribute significant polarity and serve as hydrogen-bond acceptors, while also influencing the electron distribution of the heteroaromatic system through resonance effects.

At the 8-position of the purine core is a substituted piperidinyl group. Piperidine is a saturated six-membered nitrogen-containing ring that is conformationally flexible and can adopt chair conformations. The nitrogen atom in the piperidine ring is connected to a carbamic acid tert-butyl ester group, forming a carbamate functionality. Carbamates are characterized by resonance between the nitrogen lone pair and the carbonyl group, which imparts partial double-bond character to the N–C bond and reduces the basicity of the nitrogen.

The tert-butyl group in the carbamate portion is a bulky alkyl substituent that increases steric hindrance and hydrophobic character. Carbamate tert-butyl esters are commonly used as protecting groups in synthetic chemistry due to their stability under a range of conditions and their ability to be selectively removed under acidic conditions.

At the 7-position of the purine system, the molecule contains a 2-butynyl substituent. This group contains a carbon–carbon triple bond, introducing linear geometry and increased unsaturation into the molecule. Alkynes are relatively electron-rich π-systems and can participate in certain addition reactions under appropriate conditions, although in this context they primarily contribute to structural rigidity and hydrophobic character.

At the 1-position of the purine core, there is a [(4-methyl-2-quinazolinyl)methyl] substituent. Quinazoline is a bicyclic heteroaromatic system composed of fused benzene and pyrimidine rings containing two nitrogen atoms. The presence of a methyl substituent on the quinazoline ring further modifies its electronic and steric properties. The methylene linker connecting the quinazoline to the purine introduces limited rotational flexibility while maintaining overall molecular connectivity.

The stereochemical descriptor (3R) indicates a defined configuration at the piperidine-substituted carbon center. This stereocenter plays an important role in determining the three-dimensional shape of the molecule, influencing how the purine, piperidine, and carbamate portions are spatially arranged relative to each other.

From a structural perspective, the molecule is highly rigid in its heteroaromatic regions (purine and quinazoline systems) but more flexible in its saturated piperidine and linker regions. This combination results in a hybrid conformational profile, with both fixed planar aromatic domains and adaptable aliphatic segments.

Physicochemically, the compound contains both strongly polar and hydrophobic regions. The purine dione system and multiple nitrogen atoms contribute polarity and hydrogen-bonding capability, while the tert-butyl carbamate, alkynyl chain, and aromatic hydrocarbon portions contribute hydrophobic character. This balance suggests an amphiphilic molecular profile with multiple interaction modes.

Chemically, the most reactive sites include the carbamate group, which can undergo hydrolysis under acidic or enzymatic conditions, and the carbonyl groups on the purine ring, which participate in hydrogen bonding and electronic delocalization. The alkyne group may be reactive under specialized chemical conditions, while the heteroaromatic systems are generally stable under neutral environments.

Without verified literature specific to this exact compound, no claims can be made regarding biological activity or application. Based on structural analysis alone, it is best described as a stereochemically defined, polyheterocyclic system incorporating a dioxopurine core, a quinazoline substituent, a piperidine-linked carbamate, and an alkynyl side chain, forming a highly functionalized and conformationally diverse molecular architecture.

References

2014. Linagliptin. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-12-0077