Orforglipron Intermediate N-3 2212021-82-2

Orforglipron Intermediate (CAS 2212021-82-2)

Orforglipron Intermediate (CAS 2212021-82-2)

Systematic Name:

5-((S)-2,2-Dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-1-((1S,2S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-N-phenyl-1H-indole-2-carboxamide

Common Aliases:

Orforglipron intermediates N-3

Orforglipron ACI Fragment

Orforglipron Advanced Intermediate

LY3502970 Key Building Block

Molecular Formula: C₂₉H₃₂N₄O₄

Molecular Weight: 500.59 g/mol

1. Structural Complexity & Characteristics

This compound is a highly functionalized and complex chiral molecule. Its key structural features include:

(1) Multiple Stereocenters: The molecule contains three defined stereogenic centers (two on the cyclopropane ring and one on the tetrahydropyran ring), all configured with specific (S) or (R) absolute stereochemistry. This precise control is critical for the biological activity of the final drug substance.

(2) Reactive Functional Group: The structure incorporates a 1,2,4-oxadiazol-5-one moiety. This group acts as a highly activated carboxylic acid derivative, making it exceptionally susceptible to nucleophilic attack in subsequent synthesis steps.

(3) Steric Hindrance: The presence of the N-phenyl substituted amide and the geminal dimethyl groups on the tetrahydropyran ring creates significant steric bulk around the reactive center.

2. Role in Orforglipron Synthesis

Orforglipron (LY3502970), developed by Eli Lilly, is a leading oral, non-peptide GLP-1 receptor agonist currently in advanced clinical trials for Type 2 Diabetes and Obesity.

In the multi-step convergent synthesis of Orforglipron, CAS 2212021-82-2 serves as the final advanced intermediate of the left-hand ACI (Indole) fragment. Its primary roles are:

(1) Coupling Substrate: The electrophilic oxadiazol-5-one group is designed to undergo a nucleophilic addition-elimination reaction with the right-hand ZCI fragment (e.g., the amine-containing pyrazolopyridine, CAS 2212022-56-3), facilitating the crucial ligation of the two complex fragments.

(2) Cyclization Precursor: Under specific basic conditions, this intermediate can directly participate in an intramolecular cyclization to construct the signature central imidazol-2-one core of the Orforglipron molecule.