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【结 构 式】 
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【分子编号】27603 【品名】ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-7-[2-(benzyloxy)-4-methoxyphenyl]-2-butyl-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate 【CA登记号】 |
【 分 子 式 】C36H37NO6 【 分 子 量 】579.69292 【元素组成】C 74.59% H 6.43% N 2.42% O 16.56% |
合成路线1
该中间体在本合成路线中的序号：(LIX)In a further procedure, pyridine-2,3-dicarboxylic acid (L) was esterified with MeOH and SOCl2 and then oxidized to the N-oxide (LI), which by treatement with POCl3 gave chloropyridine (LII). Then, substitution of the halogen atom of (LII) for a butyl group using n-BuLi in the presence of ZnCl2 and palladium catalyst provided butylpyridine (LIII). Saponification of the methyl esters, followed by reaction with Ac2O gave cyclic anhydride (LIV). This was condensed with organozinc reagent (LV) to give ketone (LVI). After activation of (LVI) with carbonyl diimidazole, condensation with the lithium enolate of ethyl acetate, followed by cyclization produced cyclopentenone (LVII). This was condensed with Grignard reagent (XXIV) to give (LVIII) and then reduced with Zn and HCl and isomerized in the presence of EtONa to provide (LIX) as a racemic mixture.
| 【1】 Niiyama, K.; et al.; A potent, orally active, most balanced ETA/ETB dual endothelin receptor antagonist. Discovery of J-104132. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.297. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 27570 | 1,3-benzodioxol-5-yl(bromo)magnesium | C7H5BrMgO2 | 详情 | 详情 | |
| (L) | 17246 | 2,3-pyridinedicarboxylic acid; Quinolinic Acid | 89-00-9 | C7H5NO4 | 详情 | 详情 |
| (LI) | 27595 | 2,3-bis(methoxycarbonyl)-1-pyridiniumolate | C9H9NO5 | 详情 | 详情 | |
| (LII) | 27596 | dimethyl 6-chloro-2,3-pyridinedicarboxylate | C9H8ClNO4 | 详情 | 详情 | |
| (LIII) | 27597 | dimethyl 6-butyl-2,3-pyridinedicarboxylate | C13H17NO4 | 详情 | 详情 | |
| (LIV) | 27598 | 2-butylfuro[3,4-b]pyridine-5,7-dione | C11H11NO3 | 详情 | 详情 | |
| (LV) | 27599 | [2-(benzyloxy)-4-methoxyphenyl](chloro)zinc | C14H13ClO2Zn | 详情 | 详情 | |
| (LVI) | 27600 | 2-[2-(benzyloxy)-4-methoxybenzoyl]-6-butylnicotinic acid | C25H25NO5 | 详情 | 详情 | |
| (LVII) | 27601 | ethyl 7-[2-(benzyloxy)-4-methoxyphenyl]-2-butyl-5-oxo-5H-cyclopenta[b]pyridine-6-carboxylate | C25H25NO5 | 详情 | 详情 | |
| (LVIII) | 27602 | ethyl 5-(1,3-benzodioxol-5-yl)-7-[2-(benzyloxy)-4-methoxyphenyl]-2-butyl-5-hydroxy-5H-cyclopenta[b]pyridine-6-carboxylate | C36H35NO7 | 详情 | 详情 | |
| (LIX) | 27603 | ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-7-[2-(benzyloxy)-4-methoxyphenyl]-2-butyl-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C36H37NO6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LIX)Hydrogenolysis of the benzyl ether of (LIX) and subsequent treatment with Tf2O gave aryl triflate (LX). Stille coupling reaction of (LX) with organotin reagent (LXI) produced unsaturated ester (LXII), which was then hydrogenated over Pd/C to give (LXIII). Basic hydrolysis of both ester groups of (LXIII) yielded the racemic diacid, which was finally resolved using quinidine.
| 【1】 Niiyama, K.; et al.; A potent, orally active, most balanced ETA/ETB dual endothelin receptor antagonist. Discovery of J-104132. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.297. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LIX) | 27603 | ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-7-[2-(benzyloxy)-4-methoxyphenyl]-2-butyl-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C36H37NO6 | 详情 | 详情 | |
| (LX) | 27604 | ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-(4-methoxy-2-[[(trifluoromethyl)sulfonyl]oxy]phenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C30H30F3NO8S | 详情 | 详情 | |
| (LXI) | 27605 | methyl 2-[(tributylstannyl)methyl]acrylate | C17H34O2Sn | 详情 | 详情 | |
| (LXII) | 27606 | ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[4-methoxy-2-[2-(methoxycarbonyl)-2-propenyl]phenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C34H37NO7 | 详情 | 详情 | |
| (LXIII) | 27607 | ethyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[4-methoxy-2-[(2S)-3-methoxy-2-methyl-3-oxopropyl]phenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C34H39NO7 | 详情 | 详情 |