Products

The product is Ethyl 3-(4-methoxyphenyl)-3-oxopropanoate, a β-keto ester characterized by a 4-methoxyphenyl group attached to a 3-oxopropanoate backbone. Structurally, the molecule consists of an ethyl ester at one terminus, a ketone group at the C3 position, and a para-methoxyphenyl substituent serving as the aromatic core. This β-keto ester motif confers distinctive chemical versatility, allowing participation in a broad spectrum of reactions including condensation, cyclization, Claisen condensation, Knoevenagel reaction, and Michael addition. The electron-donating methoxy group at the para position stabilizes the adjacent carbonyl system and influences the overall reactivity profile of the molecule. The presence of both an ester and a ketone functional group within the same carbon skeleton also creates a versatile scaffold for constructing heterocyclic systems such as pyrazoles, pyrimidines, and coumarins. This unique combination of structural features makes Ethyl 3-(4-methoxyphenyl)-3-oxopropanoate a valuable building block in organic synthesis and pharmaceutical development.

The product is N-(3,4-Dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)acetamide, a symmetrical amide featuring two distinct 3,4-dimethoxyphenyl units linked by a 2‑carbon ethyl spacer and an acetamide carbonyl bridge. One 3,4-dimethoxyphenyl ring is positioned at the amine terminus, connected through a flexible ethyl chain that allows the two aromatic systems to adopt optimal spatial arrangements in three dimensions. The other 3,4-dimethoxyphenyl ring is attached directly to the α‑carbon of the acetamide group, creating a rigid, planar conformation on the carbonyl side. Each phenyl ring carries two electron-donating methoxy substituents at the 3‑ and 4‑positions relative to the point of attachment, significantly enhancing the molecule‘s lipophilicity and enabling additional hydrogen‑bonding interactions through the oxygen lone pairs of the methoxy groups. The central amide linkage — featuring a planar, resonance‑stabilized C=O bond — imposes partial double‑bond character on the C–N bond, reducing conformational flexibility at the acetamide site while preserving the conformational freedom of the adjacent ethyl chain. This precise combination — one rigid and one flexible aromatic substitution pattern, a stable amide core, and four strategically placed methoxy groups — underlies the compound‘s established utility as a valuable pharmaceutical impurity reference standard.

3-Chloroaniline, with chlorine substituted at the meta position of the aniline ring (C₆H₆ClN), is a fundamental aromatic amine building block in organic synthesis. The meta relationship between the electron-withdrawing chlorine substituent and the electron-donating amino group creates a distinct electronic asymmetry that significantly influences the molecule‘s reactivity and substitution patterns — an effect not observed in its ortho and para isomers. This meta-substitution pattern lowers the electron density at the ortho and para positions relative to the amine group, suppressing unwanted side reactions while preserving the nucleophilicity of the amino group for subsequent functionalization. The molecule’s unique combination of moderate polarity (logP ~0.77–2.03), high thermal stability (boiling point 230–231°C) and a reactive primary amine enables it to serve as a versatile electrophile — through diazonium salt formation — and nucleophile — through amide or urea bond formation — all within a single synthetic workflow.

Orforglipron Impurity 18 (CAS 2212022-56-3) is a key intermediate and related impurity of the novel oral non‑peptide GLP‑1 receptor agonist Orforglipron, developed for the treatment of type 2 diabetes and obesity.From a structural perspective, this molecule features a complex polyheterocyclic scaffold. The core comprises an imidazol‑2‑one ring fused to a tetrahydro‑pyrazolo[4,3‑c]pyridine system, which is further substituted with a 4‑fluoro‑1‑methyl‑1H‑indazole moiety and a 4‑fluoro‑3,5‑dimethylphenyl group. The presence of two fluorine atoms enhances metabolic stability and lipophilicity, while the chiral center at the tetrahydropyridine ring (S‑configuration) is crucial for the biological activity of the final drug. The molecular framework allows precise interaction with the GLP‑1 receptor, and this intermediate serves as an essential building block in the multi‑step synthesis of Orforglipron.

Orforglipron Impurity 17, chemically designated as 5-[(S)-2,2-dimethyltetrahydro-2H-pyran-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl]-1H-indole-2-carboxylic acid, represents a highly intricate and functionally diverse intermediate in the Orforglipron synthetic cascade. The structural framework is anchored by a 1H-indole-2-carboxylic acid core, a privileged bicyclic scaffold widely recognized for its prevalence in pharmacologically active molecules, contributing to target binding affinity through π-stacking and hydrogen bond interactions.The indole nitrogen is strategically substituted with a chiral (1S,2S)-cyclopropyl moiety bearing a 5‑oxo‑4,5‑dihydro‑1,2,4‑oxadiazol-3-yl group—a heterocyclic motif frequently associated with enhanced metabolic stability and favorable pharmacokinetic properties. At the indole 5‑position, an (S)-configured 2,2-dimethyltetrahydropyran ring introduces both lipophilicity and steric bulk, while the carboxylic acid functionality provides a handle for subsequent amidation or esterification in the route to the final API. With three distinct chiral centers, Orforglipron Impurity 17 demands stringent stereochemical control during synthesis, and its comprehensive characterization is therefore indispensable for ensuring the quality and consistency of the final drug product.

Orforglipron Impurity 20, chemically known as 1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-5-[(4S)-2,2-dimethyltetrahydro-2H-pyran-4-yl]-N-methyl-N-phenyl-1H-indole-2-carboxamide (CAS 2212021-81-1), represents a sophisticated intermediate in the synthetic pathway of the oral GLP-1 receptor agonist Orforglipron. From a structural perspective, this molecule features a 1H-indole-2-carboxamide core, a bicyclic aromatic system that provides rigidity and facilitates receptor binding. The indole nitrogen is functionalized with a (1S,2S)-1-cyano-2-methylcyclopropyl group, introducing a strained three‑membered ring bearing a nitrile functionality—a motif that contributes to metabolic stability and stereochemical precision. Additionally, a tetrahydropyran ring with two geminal methyl groups is attached at the indole 5‑position with (S)‑configuration, while the carboxamide nitrogen carries both a methyl and a phenyl substituent. The presence of three chiral elements—the (S)‑tetrahydropyran and the (1S,2S)‑cyclopropyl stereocenters—makes Orforglipron Impurity 20 a structurally complex and stereochemically demanding molecule that is essential for ensuring the correct spatial orientation required for subsequent synthetic transformations leading to the final API.