【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 |