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【结 构 式】 
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【分子编号】29947 【品名】ethyl 2-oxocyclopentanecarboxylate 【CA登记号】611-10-9 |
【 分 子 式 】C8H12O3 【 分 子 量 】156.18148 【元素组成】C 61.52% H 7.74% O 30.73% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of ethyl 2-oxocyclopentanecarboxylate (I) with ethyl 2-(4-chloromethylphenyl)propionate (II) by means of KOH in hot DMF gives ethyl 2-[4-(1-ethoxycarbonyl-2-oxocyclopentan-1-ylmethyl)phenyl]propionate (III), which is then hydrolyzed and decarboxylated by treatment with 47% HBr in refluxing dioxane.
| 【1】 Misaka, E.; Terada, A.; Wachi, K. (Sankyo Co., Ltd.); Substituted phenylacetic acid derivatives and process for the preparation thereof. DE 2814556; ES 468578; FR 2395256; GB 1580113; US 4161538 . |
| 【2】 Castaner, J.; Serradell, M.N.; Loxoprofen. Drugs Fut 1984, 9, 1, 22. |
合成路线2
该中间体在本合成路线中的序号：(I)Condensation of ethyl cyclopentanone-2-carboxylate (I) with pyrazolyl amine (II) in boiling AcOH produced pyrazolopyrimidinol (III), which was then chlorinated by means of POCl3 to give (IV). Finally, displacement of the chlorine atom of (IV) with piperazine in hot DMF furnished the title compound.
| 【1】 Stadler, H.; Boes, M.; Riemer, C. (F. Hoffmann-La Roche AG); Pyrazolopyrimidines and pyrazolotriazines with 5-HT6 receptor affinity. EP 0941994; JP 2000186090 . |
| 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) | 29947 | ethyl 2-oxocyclopentanecarboxylate | 611-10-9 | C8H12O3 | 详情 | 详情 |
| (II) | 33690 | 3-(methylsulfanyl)-4-(phenylsulfonyl)-1H-pyrazol-5-ylamine; 3-(methylsulfanyl)-4-(phenylsulfonyl)-1H-pyrazol-5-amine | C10H11N3O2S2 | 详情 | 详情 | |
| (III) | 33691 | 2-(methylsulfanyl)-3-(phenylsulfonyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidin-8-ol | C16H15N3O3S2 | 详情 | 详情 | |
| (IV) | 33692 | 8-chloro-2-(methylsulfanyl)-3-(phenylsulfonyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine; 8-chloro-2-(methylsulfanyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidin-3-yl phenyl sulfone | C16H14ClN3O2S2 | 详情 | 详情 | |
| (V) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Condensation between ethyl 2-oxocyclopentanecarboxylate (I) and thiourea (II) gives rise to the thiouracil derivative (III) (1,2). This is then alkylated with 4-fluorobenzyl chloride (IV) to yield thioether (V). Subsequent alkylation of (V) with tert-butyl iodoacetate (VI) furnishes adduct (VII). Further acidic cleavage of the tert-butyl ester group of (VII) leads to carboxylic acid (VIII) (2,3). Alternatively, intermediate (VIII) is prepared by alkylation of (V) with triflate (IX), followed by alkaline hydrolysis of the resultant methyl ester (X)
| 【1】 The identification of clinical candidate SB-480848: A potent inhibitor of lipoprotein-associated phospholipase A2. Bioorg Med Chem Lett 2003, 13, 6, 1067. |
| 【2】 Ife, R.J.; Leach, C.A.; Hickey, D.M.B.; Pinto, I.L.; Smith, S.A.; Stanway, S.J. (GlaxoSmithKline plc); Pyrimidine-4-one derivs. as LDL-PLA 2 inhibitors. EP 1263740; JP 2003523335; US 2002103213; US 6649619; WO 0160805 . |
| 【3】 Mulholland, K.R.; Ross, A.R.; Smith, G.E.; Slater, G.R. (GlaxoSmithKline plc); Novel processes. WO 0316287 . |
| 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) | 29947 | ethyl 2-oxocyclopentanecarboxylate | 611-10-9 | C8H12O3 | 详情 | 详情 |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 63490 | 2-sulfanyl-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one | C7H8N2OS | 详情 | 详情 | |
| (IV) | 12354 | 4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene | 352-11-4 | C7H6ClF | 详情 | 详情 |
| (V) | 63491 | 2-{[(4-fluorophenyl)methyl]sulfanyl}-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one | C14H13FN2OS | 详情 | 详情 | |
| (VI) | 24735 | tert-Butyl 2-iodoacetate | C6H11IO2 | 详情 | 详情 | |
| (VII) | 63492 | 1,1-dimethylethyl 2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetate | C20H23FN2O3S | 详情 | 详情 | |
| (VIII) | 63494 | 2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid | C16H15FN2O3S | 详情 | 详情 | |
| (IX) | 63493 | methyl 2-{[(trifluoromethyl)sulfonyl]oxy}acetate | C4H5F3O5S | 详情 | 详情 | |
| (X) | 63495 | methyl 2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetate | C17H17FN2O3S | 详情 | 详情 |