Synthesis of the stabilized active metabolite of clopidogrel |
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Authors: | Guillaume Bluet,Jorg Blankenstein,Eric Brohan,Cé line Pré vost,Michel Chevé ,Joseph Schofield,Sé bastien Roy |
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Affiliation: | 1. SANOFI R&D, Isotope Chemistry and Metabolite Synthesis (ICMS)—SCP DSAR/DD Paris, 1 avenue Pierre Brossolette, Chilly-Mazarin 91385 Cedex, France;2. SANOFI R&D, Analytical Sciences – SCP LGCR AnSci Paris, 13 quai Jules Guesdes, Vitry-sur-Seine, 94403 Cedex, France |
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Abstract: | The convergent synthesis of the stabilized active metabolite of clopidogrel was achieved in eleven steps from commercially available 1,2,3,6-tetrahydropyridine and 2-bromo-3′-methoxy acetophenone (MPBr). This synthetic route used a standard Horner–Wadsworth–Emmons reaction allowing the introduction of a Z exocyclic double bond. A selective hydrolysis of an acrylic methyl ester moiety, isolated by an efficient and reliable preparative chiral chromatography at gram scale, released the title compound with a 98% LC purity and d.e. >99%. |
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Keywords: | Clopidogrel Thienopyridine Metabolism Horner&ndash Wadsworth&ndash Emmons Preparative chiral HPLC |
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