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【结 构 式】

【药物名称】MRS-1486

【化学名称】4-Ethyl-5-(ethylsulfanylcarbonyl)-2-phenyl-6-propylpyridine-3-carboxylic acid ethyl ester

【CA登记号】212329-39-0

【 分 子 式 】C22H27NO3S

【 分 子 量 】385.52939

【开发单位】National Institutes of Health (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Adenosine A3 Antagonists, Antiinflammatory Drugs

合成路线1

Acylation of Meldrum's acid (I) with butyryl chloride (II) in the presence of pyridine gave butyryl derivative (III). Subsequent ring opening of (III) with ethanethiol (IV), followed by decarboxylation provided S-ethyl 3-oxothiocaproate (V). Ethyl 3-amino-3-phenyl-2-propenoate (VII) was prepared by reaction of benzoylacetate (VI) with ammonium acetate in refluxing ethanol. Then, Hantzsch condensation of ketothioester (V), b-enaminoester (VII), and propionaldehyde (VIII) in EtOH at 80 C in a sealed tube furnished the dihydropyridine (IX). Finally, oxidation of (IX) using chloranil (X) in boiling THF gave the target pyridine.

1 Li, A.-H.; Moro, S.; Melman, N.; Ji, X.D.; Jacobson, K.A.; Structure-activity relationships and molecular mod. J Med Chem 1998, 41, 17, 3186.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 14738 Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione;Malonic acid cyclic isopropylidene ester 2033-24-1 C6H8O4 详情 详情
(II) 10792 Butanoyl chloride; Butyryl chloride 141-75-3 C4H7ClO 详情 详情
(III) 23711 5-butyryl-2,2-dimethyl-1,3-dioxane-4,6-dione C10H14O5 详情 详情
(IV) 23712 1-ethanethiol; ethylhydrosulfide 75-08-1 C2H6S 详情 详情
(V) 23713 S-ethyl 3-oxohexanethioate C8H14O2S 详情 详情
(VI) 10004 Ethyl 3-oxo-3-phenylpropanoate; Benzoylacetic acid, ethyl ester 94-02-0 C11H12O3 详情 详情
(VII) 23715 ethyl (E)-3-amino-3-phenyl-2-propenoate C11H13NO2 详情 详情
(VIII) 15966 propionaldehyde 123-38-6 C3H6O 详情 详情
(IX) 23716 ethyl 4-ethyl-5-[(ethylsulfanyl)carbonyl]-2-phenyl-6-propyl-1,4-dihydro-3-pyridinecarboxylate C22H29NO3S 详情 详情
(X) 21891 2,3,5,6-Tetrachloro-1,4-benzoquinone; 2,3,5,6-Tetrachlorobenzo-1,4-quinone; p-Chloranil 118-75-2 C6Cl4O2 详情 详情
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