A convenient synthetic method of a 5,7-diarylcyclopenteno-[1,2-b]pyridine-6-carboxylate: a key intermediate for potent endothelin receptor antagonists.
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.
Niiyama
Kenji
K
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki, Japan. niiymakj@banyu.co.jp
Yoshizumi
Takashi
T
Takahashi
Hirobumi
H
Naya
Akira
A
Ohtake
Norikazu
N
Fukami
Takehiro
T
Mase
Toshiaki
T
Hayama
Takashi
T
Ishikawa
Kiyofumi
K
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
D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D007202:Indicators and Reagents; D007651:Keto Acids; D011725:Pyridines; D012997:Solvents; D015032:Zinc