Orforglipron Intermediate N-2 2212022-56-3

Orforglipron Intermediate (CAS 2212022-56-3)

Orforglipron Intermediate (CAS 2212022-56-3)

Systematic Name:

(S)-1-(4-Fluoro-1-methyl-1H-indazol-5-yl)-3-(2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3-yl)-1H-imidazol-2(3H)-one

Common Aliases:

Orforglipron ZCI Fragment

Orforglipron Intermediate 18 / Impurity 18

LY3502970 Key Intermediate

1. Structural Complexity & Characteristics

This compound is a structurally sophisticated polycyclic heterocyclic intermediate. Its key structural features include:

(1) Chiral Center: Contains one stereogenic center with an absolute configuration of (S), which is critical for ensuring the biological activity of the final drug substance.

(2) Difluoro Substitution: Incorporates two fluorine atoms located on the indazole ring and the phenyl ring, respectively. This modification is typically employed to enhance metabolic stability and lipophilicity.

(3) Fused Heterocyclic System: Integrates three key pharmacophores: an indazole, a pyrazolo[4,3-c]pyridine, and an imidazol-2-one core.

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 2212022-56-3 serves as a critical precursor/building block for the right-hand ZCI (Imidazolin-2-one) fragment. It is designed to undergo subsequent coupling reactions with the left-hand ACI (Indole) fragment (e.g., CAS 2212021-81-1) to construct the complete macrocyclic structure of the active pharmaceutical ingredient (API).