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【结 构 式】 
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【分子编号】25533 【品名】2-Hydroxy-4-(4-methoxyphenyl)-3-oxo-2(E)-butenoic acid ethyl ester lithium salt 【CA登记号】 |
【 分 子 式 】C13H13LiO5 【 分 子 量 】256.18422 【元素组成】C 60.95% H 5.11% Li 2.71% O 31.23% |
合成路线1
该中间体在本合成路线中的序号：(II)Title compound has been prepared by several routes: Condensation of 4'-methoxyacetophenone (I) with diethyl oxalate in the presence of lithium hexamethyldisilazide provided lithium ethyl 4-methoxybenzoylpyruvate (II). Subsequent condensation of (II) with 4-methoxyphenylhydrazine hydrochloride (III) yielded diarylpyrazole (IV). This was coupled with bromide (V) in the presence of n-BuLi to afford ketone (VI). The oxazoline ring of (VI) was then hydrolyzed to carboxylic acid (VII) by successive treatments with HCl and with NaOH. Activation of the carboxylic acid of (VII) as the mixed anhydride with ethyl chloroformate, followed by treatment with gaseous ammonia provided amide (VIII). The required dimethyl ketal was finally introduced in (VIII) by means of trimethyl orthoformate in MeOH in the presence of p-TsOH.
| 【1】 Lamari, L.; Zitouni, A.; Boudjella, H.; et al.; J Heterocycl Chem 1989, 26, 8, 1389-1392. |
| 【2】 Numata, H.; Okamoto, Y.; Shinoda, M.; Kobayashi, N.; Miyazawa, S.; Kawahara, T.; Shirota, H.; Nagakura, N.; Horizoe, T.; Abe, S.; Kobayashi, S.; Yamanaka, T. (Eisai Co., Ltd.); Pyrazole derivs. exhibiting anti-inflammatory and analgesic effects. JP 1998509140; WO 9614302 . |
| 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) | 11041 | 4-Methoxyacetophenone; 1-(4-Methoxyphenyl)-1-ethanone | 100-06-1 | C9H10O2 | 详情 | 详情 |
| (II) | 25533 | 2-Hydroxy-4-(4-methoxyphenyl)-3-oxo-2(E)-butenoic acid ethyl ester lithium salt | C13H13LiO5 | 详情 | 详情 | |
| (III) | 12688 | 4-Hydrazinophenyl methyl ether; 1-(4-Methoxyphenyl)hydrazine | 3471-32-7 | C7H10N2O | 详情 | 详情 |
| (IV) | 25534 | ethyl 1,5-bis(4-methoxyphenyl)-1H-pyrazole-3-carboxylate | C20H20N2O4 | 详情 | 详情 | |
| (V) | 25535 | 2-(5-bromo-2-chlorophenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole | C11H11BrClNO | 详情 | 详情 | |
| (VI) | 25536 | [1,5-bis(4-methoxyphenyl)-1H-pyrazol-3-yl][4-chloro-3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]methanone | C29H26ClN3O4 | 详情 | 详情 | |
| (VII) | 25537 | 5-[[1,5-bis(4-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl]-2-chlorobenzoic acid | C25H19ClN2O5 | 详情 | 详情 | |
| (VIII) | 25538 | 5-[[1,5-bis(4-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl]-2-chlorobenzamide | C25H20ClN3O4 | 详情 | 详情 |