(S)-1-(cyanomethyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-indole-2-carboxamide
[CAS 2212021-80-0]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: (S)-1-(cyanomethyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-indole-2-carboxamide
• Synonyms: 1-(cyanomethyl)-5-[(4S)-2,2-dimethyloxan-4-yl]-N-methyl-N-phenylindole-2-carboxamide
• Molecular Formula: C₂₅H₂₇N₃O₂
• Molecular Weight: 401.50
• CAS Registry Number: 2212021-80-0
• SMILES: CC1(C[C@H](CCO1)C2=CC3=C(C=C2)N(C(=C3)C(=O)N(C)C4=CC=CC=C4)CC#N)C

Discovery and Applications

(S)-1-(cyanomethyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-indole-2-carboxamide is a highly substituted indole-derived carboxamide containing multiple functional motifs, including an indole heteroaromatic core, a tertiary amide, a nitrile-containing side chain, and a substituted tetrahydropyran ring. The structure combines rigid aromatic regions with conformationally flexible saturated components, producing a chemically diverse molecular framework.

The central structural element is the indole nucleus, a fused bicyclic aromatic system composed of a benzene ring fused to a pyrrole ring. Indole is an electron-rich heteroaromatic scaffold because the pyrrolic nitrogen contributes its lone-pair electrons to aromatic delocalization. In this molecule, however, the indole nitrogen is substituted with a cyanomethyl group, eliminating the NH hydrogen that would otherwise function as a hydrogen-bond donor.

The 1-position substitution consists of a cyanomethyl group (–CH₂CN). The nitrile functionality contains a carbon–nitrogen triple bond and is strongly polarized because of the electronegativity of nitrogen. Nitriles are generally chemically stable under neutral conditions and function primarily as hydrogen-bond acceptors rather than donors. The nitrile group also acts as an electron-withdrawing substituent, affecting electron distribution within the adjacent molecular framework.

At the 2-position of the indole system, the structure contains a carboxamide functionality. The amide nitrogen bears both methyl and phenyl substituents, creating a tertiary amide. Because the nitrogen is fully substituted, the amide cannot donate hydrogen bonds, although the carbonyl oxygen remains a strong hydrogen-bond acceptor. The amide bond exhibits resonance stabilization between the carbonyl group and nitrogen atom, resulting in partial double-bond character and restricted rotational freedom.

The phenyl substituent attached to the amide nitrogen contributes hydrophobicity and aromatic surface area. Aromatic rings can participate in π–π interactions and hydrophobic contacts. The methyl substituent on the amide nitrogen modifies steric and electronic properties around the amide region.

At the 5-position of the indole ring, the molecule contains a substituted tetrahydropyran group, specifically a 2,2-dimethyltetrahydro-2H-pyran moiety attached through its 4-position. Tetrahydropyran is a saturated six-membered cyclic ether containing one oxygen atom within the ring. The oxygen atom contributes localized polarity and hydrogen-bond-accepting capability. The two methyl groups at the 2-position increase steric bulk and hydrophobic character while influencing preferred ring conformations.

The descriptor (S) indicates the presence of a defined stereogenic center. Stereochemistry is important because it establishes a specific three-dimensional arrangement of substituents that can influence molecular recognition and conformational behavior. The tetrahydropyran ring generally adopts chair-like conformations that minimize steric strain.

From a physicochemical perspective, the molecule contains both polar and hydrophobic regions. The indole and phenyl rings contribute extensive aromatic hydrophobic character, whereas the amide carbonyl, ether oxygen, and nitrile group provide polarity and hydrogen-bond-accepting sites. The overall molecule therefore exhibits amphiphilic characteristics.

Chemically, the most reactive sites include the amide functionality under strongly hydrolytic conditions and the indole aromatic system, which can undergo electrophilic substitution under appropriate conditions. The nitrile group is generally stable but may undergo transformation under strong hydrolytic or reductive conditions.

Without verified literature specific to this exact compound, no claims can be made regarding biological activity or practical application. Based solely on structural chemistry, it is best described as a chiral indole-derived tertiary carboxamide incorporating a nitrile-containing side chain, a substituted cyclic ether, and multiple aromatic regions that together create a structurally complex amphiphilic framework.

References

2024. Heterocyclic glp-1r agonists. US-2025304572-A1 Priority Date: 2024-03-29.
URL: https://patents.google.com/patent/US2025304572A1

2023. Glp-1 receptor targeting compounds and uses thereof. WO-2025119206-A1 Priority Date: 2023-12-05.
URL: https://patents.google.com/patent/WO2025119206A1