Polymer-assited solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia™)

Organic and Biomolecular Chemistry

Volumn 1, Issue 24, 2003, Pages 4392-4395

  Li, Xin ^a   Abell, Chris ^a   Warrington, Brian H ^a   Ladlow, Mark ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC COMPOUNDS; COLUMN CHROMATOGRAPHY; DECOMPOSITION; EVAPORATION; FILTRATION; HIGH PRESSURE LIQUID CHROMATOGRAPHY; IRRADIATION; MICROWAVES; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OXIDATION; PURIFICATION; RESINS; SYNTHESIS (CHEMICAL); THIN LAYER CHROMATOGRAPHY;

POLYMER ASSISTED SOLUTION PHASE (PASP) SYNTHESIS; SOLID PHASE ORGANIC SYNTHESIS (SPOS);

DRUG PRODUCTS;

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANTIDIABETIC AGENT; POLYMER; ROSIGLITAZONE;

ARTICLE; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; COMBINATORIAL CHEMISTRY; ISOLATION AND PURIFICATION; METHODOLOGY; SOLUTION AND SOLUBILITY; SYNTHESIS;

COMBINATORIAL CHEMISTRY TECHNIQUES; HYPOGLYCEMIC AGENTS; MODELS, CHEMICAL; MOLECULAR STRUCTURE; POLYMERS; SOLUTIONS; THIAZOLIDINEDIONES;

EID: 0347537933     PISSN: 14770520     EISSN: None     Source Type: Journal    
DOI: 10.1039/b307549d     Document Type: Article

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33. We found that this 1,4-reduction could also be mediated using aqueous sodium dithionite, however the procedure proved to be difficult to reproduce reliably and therefore catalytic hydrogenation under forcing conditions was preferred.
34. According to the reported procedure in ref. 2b, Rosiglitazone was obtained in 31% overall yield as compared to 46% overall yield in the present synthesis.
35. 1H NMR spectroscopy was more indicative of the purity of synthetic intermediates than LC-MS since many of the compounds are quite polar and tend to elute close to the origin using conventional RP-HPLC methods and solvent gradients.