8-Bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-dione
[CAS 853029-57-9]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: 8-Bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-dione
• Synonyms: 1-[(4-Methylquinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromoxanthine
• Molecular Formula: C₂₀H₁₇BrN₆O₂
• Molecular Weight: 453.29
• CAS Registry Number: 853029-57-9
• EC Number: 922-028-0
• SMILES: CC#CCN1C2=C(N=C1Br)N(C(=O)N(C2=O)CC3=NC4=CC=CC=C4C(=N3)C)C

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 602.9±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 318.4±34.3 °C (Calc.)^*
• Index of refraction: 1.713 (Calc.)^*

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

Safety Data

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

Discovery and Applications

8-Bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-dione is a highly substituted purine-2,6-dione derivative belonging to the xanthine-related heterocyclic family. Structurally, it is based on a purine scaffold bearing two carbonyl groups at positions 2 and 6, which defines the imide-like xanthine core and contributes to strong electron withdrawal and resonance stabilization within the bicyclic heteroaromatic system.

The central purine framework consists of a fused imidazole–pyrimidinedione system that is largely planar due to conjugation between ring atoms and carbonyl groups. The 3,7-dihydro designation indicates partial saturation at specific nitrogen positions, which disrupts full aromaticity but retains a conjugated heterocyclic system. This balance of aromatic and partially saturated character influences both molecular geometry and electronic distribution.

At position 8 of the purine core, a bromine atom is present. Bromine is a large, polarizable halogen substituent that exerts a strong inductive electron-withdrawing effect. Its presence increases the electrophilic character of the heterocycle and can influence binding interactions in biological or chemical contexts. The C–Br bond also represents a potential site for further functionalization in synthetic chemistry through metal-catalyzed coupling reactions.

At position 7, the molecule bears a 2-butyn-1-yl substituent, which is an alkyne-containing side chain. This group introduces linear geometry and sp-hybridized carbon atoms, contributing rigidity and hydrophobic character. The carbon–carbon triple bond is electron-rich in its π-systems and can participate in addition reactions or serve as a handle for click chemistry-type transformations under appropriate conditions. The alkynyl chain also increases conformational flexibility relative to rigid aromatic substituents.

At position 3, a methyl group is present, which provides mild electron donation through inductive effects and increases hydrophobicity. This small substituent also influences steric environment near the purine core, potentially affecting molecular conformation and intermolecular interactions.

At position 1, the purine nitrogen is substituted with a [(4-methyl-2-quinazolinyl)methyl] group. This is a bulky heteroaromatic substituent consisting of a quinazoline ring system linked via a methylene bridge. The quinazoline moiety is a fused bicyclic aromatic system containing two nitrogen atoms, contributing electron-deficient aromatic character. The methyl group on the quinazoline further modifies its electron density and steric profile.

The methylene linker provides flexibility between the purine core and the quinazoline system, allowing rotational freedom and reducing steric strain. This flexible connection enables multiple conformations in solution, influencing how the molecule may interact with binding environments.

The overall molecule contains multiple heteroatoms, including nitrogen and oxygen atoms in the purine core, as well as additional nitrogen atoms in the quinazoline substituent. These heteroatoms contribute to hydrogen bonding capacity and influence dipole distribution across the molecule.

From a physicochemical perspective, the compound is highly lipophilic due to its multiple aromatic and heteroaromatic rings, alkyl substituents, and halogen atom. However, the presence of carbonyl groups and ring nitrogens introduces localized polarity and hydrogen bond acceptor sites. This combination yields an amphiphilic but predominantly hydrophobic molecule.

Chemically, the most reactive site is the carbon–bromine bond, which can undergo substitution or cross-coupling reactions under appropriate catalytic conditions. The carbonyl groups at positions 2 and 6 are relatively stable but participate in resonance stabilization and hydrogen bonding interactions. The alkyne substituent may also undergo addition reactions under specific chemical environments.

The purine-2,6-dione core is structurally related to biologically active xanthine derivatives, although substitution pattern here significantly alters its electronic and steric properties. The fused heterocyclic system remains rigid and planar, providing a stable scaffold for substituent orientation.

Overall, 8-Bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-dione is a complex, highly substituted purine derivative featuring a halogenated xanthine-like core, an alkynyl side chain, and a bulky quinazoline-based substituent. Its structure combines rigidity, electron-rich and electron-poor aromatic systems, and multiple reactive functional groups, giving it distinct structural and chemical characteristics typical of advanced heterocyclic synthetic intermediates.

References

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