title: A convenient synthetic method of a 5,7-diarylcyclopenteno-[1,2-b]pyridine-6-carboxylate: a key intermediate for potent endothelin receptor antagonists.
abstract: A convenient method for the synthesis of the title intermediate 4 was described. The key steps of this synthesis involved: (1) regioselective addition reaction of arylzinc reagent to quinolic anhydride in 42% isolated yield, (2) conversion of a ketoacid to an enone, which was achieved in 65% yield by intramolecular Knoevenagel reaction of beta-ketoester generated by condensation of an acid imidazolide with an ester enolate, followed by dehydration assisted with silica gel, and (3) stereoselective reduction of an allyl alcohol in 75% yield with zinc under acidic conditions. This synthesis enabled us to provide hundreds of grams of without chromatographic purification.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki, Japan. niiymakj@banyu.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Niiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Naya
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohtake
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mase
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayama
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ishikawa
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002384:Catalysis; D065128:Endothelin Receptor Antagonists; D007202:Indicators and Reagents; D007651:Keto Acids / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis*; D012997:Solvents; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D007202:Indicators and Reagents; D007651:Keto Acids; D011725:Pyridines; D012997:Solvents; D015032:Zinc