【结 构 式】 |
【药物名称】AH-23848 【化学名称】[1alpha(Z),2beta,5alpha]-(±)-7-[5-[[(1,1'-Biphen-yl)-4-yl]methoxy]-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid 【CA登记号】81443-73-4 【 分 子 式 】C29H35NO5 【 分 子 量 】477.606 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Prostanoid TP (Thromboxane A2) Antagonists |
合成路线1
The reaction of bicyclo[3.2.0]hept-2-en-6-one (I) with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) in acetic acid gives 3-endo-acetoxy-2-exo-bromo-bicyclo[3.2.0]heptan-6-one (II), which is treated with morpholine in dichloromethane to yield 5-endo-acetoxy-7-anti morpholinobicyclo[2.2.l]heptan-2-one (III). Hydrolysis of (III) with NaOH gives the norbornanone (IV), which is alkylated with biphenyl methylbromide under phase transfer catalysis to give 5-endo[(1,1'-biphenyl)-4 yl]methoxy-7-anti-morpholinobicyclo[2.2.1]heptan 2-one (V). Baeyer-Villiger oxidation followed by partial reduction with diisobutylaluminum hydride (Dibal) gives the aldehyde (VI), which is then homologated to the aldehyde (VII) using methoxymethylenetriphenyl phosphorane and subsequent treatment with 2N HCl. Condensation of (VII) with 3 carboxypropyl triphenylphosphorane in tetrahydrofuran affords the acid (VIII). Finally, this compound is oxidized with Jones' reagent.
【1】 Lumley, P.; AH-23848. Drugs Fut 1986, 11, 2, 85. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
(A) | 24427 | 6-(2-[1,1'-biphenyl]-4-ylethoxy)-8-(4-morpholinyl)-2-oxabicyclo[3.2.1]octan-3-one | C25H29NO4 | 详情 | 详情 | |
(I) | 24421 | (1S,5R)bicyclo[3.2.0]hept-2-en-6-one | C7H8O | 详情 | 详情 | |
(II) | 24422 | 3-Acetoxy-2-bromobicyclo[3,2,0]hept-2-en-6-one | C8H9BrO | 详情 | 详情 | |
(III) | 24424 | 5(endo)-Acetoxy-7(R)-(4-morpholinyl)bicyclo[2,2,1]heptan-2-one | C12H19NO2 | 详情 | 详情 | |
(IV) | 24425 | 5-hydroxy-7-(4-morpholinyl)bicyclo[2.2.1]heptan-2-one | C11H17NO3 | 详情 | 详情 | |
(V) | 24426 | 5-(2-[1,1'-biphenyl]-4-ylethoxy)-7-(4-morpholinyl)bicyclo[2.2.1]heptan-2-one | C25H29NO3 | 详情 | 详情 | |
(VI) | 24428 | 2-[(1R,2R,3R,5S)-5-(2-[1,1'-biphenyl]-4-ylethoxy)-3-hydroxy-2-(4-morpholinyl)cyclopentyl]acetaldehyde | C25H31NO4 | 详情 | 详情 | |
(VII) | 24429 | 3-[(1R,2R,3R,5S)-5-(2-[1,1'-biphenyl]-4-ylethoxy)-3-hydroxy-2-(4-morpholinyl)cyclopentyl]propanal | C26H33NO4 | 详情 | 详情 | |
(VIII) | 24431 | (E)-6-[(1R,2R,3R,5S)-5-(2-[1,1'-biphenyl]-4-ylethoxy)-3-hydroxy-2-(4-morpholinyl)cyclopentyl]-3-hexenoic acid | C29H37NO5 | 详情 | 详情 | |
(C) | 24430 | 3-Carboxypropyltriphenylphosphonium bromide | C22H23BrO2P | 详情 | 详情 |