Velpatasvir intermediate

China [CN]

1. Basic Physical and Chemical Properties and Structural Characterization

Appearance: White crystalline powder, odorless;

Solubility: Slightly soluble in water, readily soluble in DMSO, DMF, ethyl acetate, slightly soluble in methanol;

Chiral characteristics: Contains 5 consecutive chiral centers (2S,4S/2S,5S/2S), which are key nodes for stereoselective control of Velpatasvir;

Stability: Stable at room temperature and dry conditions, sensitive to acid (BOC protecting group is easily removed), strong acidic conditions (pH<3) should be avoided.

2. Key Role in the Synthesis Pathway (Industrial Route)

Core Coupling: The chromene-naphthalene-imidazole fragment (brominated) is coupled with valine-pyrrolidine amide via Suzuki coupling to introduce the imidazole side chain, forming the core structure;

Chiral Side Chain Introduction: The core structure is condensed with BOC-chiral pyrrolidine ester (1378391-45-7) via condensation reaction (EDCI/HOBt) to construct the chiral pyrrolidine-imidazole-chromene-naphthalene-imidazole skeleton of Velpatasvir;

Deprotection and Purification: The BOC protecting group is removed with trifluoroacetic acid (TFA), followed by methylation and recrystallization (ethanol-water system) to obtain Velpatasvir free base, with a total yield of approximately 35-40% (based on 1378391-45-7).