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【结 构 式】 
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【分子编号】11335 【品名】tert-butyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (tert-Butoxycarbonylmethylene)triphenylphosphorane 【CA登记号】35000-38-5 |
【 分 子 式 】C24H25O2P 【 分 子 量 】376.435062 【元素组成】C 76.58% H 6.69% O 8.5% P 8.23% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 2-(7-chloro-1,8-naphthyrin-2-yl)-3-hydroxyisoindolin-1-one (I) with tert-butoxycarbonylmethylenetriphenylphosphorane (II) in refluxing toluene gives 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxoisoindolin-1-acetic acid tert-butyl ester (III), which is hydrolyzed with trifluoroacetic acid to the corresponding free acid (IV). Finally, this compound is condensed with 1,4-dioxa-8-azaspiro[4.5]decane (V) by means of diethyl phosphorocyanidate and triethylamine in DMF.
| 【1】 Okada, T.; Mohler, M.; Benzodiazepine receptor: Demonstration in the central nervous system. Science 1977, 198, 849-51. |
| 【2】 Goto, G.; Saji, Y. (Takeda Chemical Industries, Ltd.); Isoindolinone derivs., production and use thereof. EP 0174858; JP 1986069773; JP 1990262578; JP 1992364180; US 4778801 . |
| 【3】 Graul, A.; Prous, J.; Castaner, J.; DN-2327. Drugs Fut 1993, 18, 5, 414. |
| 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) | 11334 | 2-(7-Chloro[1,8]naphthyridin-2-yl)-3-hydroxy-1-isoindolinone | C16H10ClN3O2 | 详情 | 详情 | |
| (II) | 11335 | tert-butyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (tert-Butoxycarbonylmethylene)triphenylphosphorane | 35000-38-5 | C24H25O2P | 详情 | 详情 |
| (III) | 11336 | tert-butyl 2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]acetate | C22H20ClN3O3 | 详情 | 详情 | |
| (IV) | 11337 | 2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]acetic acid | C18H12ClN3O3 | 详情 | 详情 | |
| (V) | 11338 | 1,4-Dioxa-8-azaspiro[4.5]decane; 4-Piperidone ethylene ketal | 177-11-7 | C7H13NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The Wittig condensation of o-phthalaldehyde (I) with tert-butyl triphenylphosphoranylideneacetate (II) in methylene chloride gives tert-butyl 3-(2-formylphenyl)-2(E)-propenoate (III), which is then cyclized with ethyl 3-aminocrotonate (IV) in acetic acid.
| 【1】 Borthwick, A.D.; Pierccioli, D.; Micheli, D.; Semeraro, C.; Gaviraghi, G. (Glaxo SpA); 1,4-dihydropyridines.. ES 8703839; ES 8703839; US 4801599; US 5011848 . |
| 【2】 Prous, J.; Castaner, J.; LACIDIPINE < Rec INN; BAN; USAN >. Drugs Fut 1989, 14, 4, 317. |
| 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) | 19472 | o-phthalaldehyde; o-phthaldialdehyde; phthalaldehyde | 643-79-8 | C8H6O2 | 详情 | 详情 |
| (II) | 11335 | tert-butyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (tert-Butoxycarbonylmethylene)triphenylphosphorane | 35000-38-5 | C24H25O2P | 详情 | 详情 |
| (III) | 19474 | tert-butyl (E)-3-(2-formylphenyl)-2-propenoate | C14H16O3 | 详情 | 详情 | |
| (IV) | 11975 | Ethyl (E)-3-amino-2-butenoate | 7318-00-5 | C6H11NO2 | 详情 | 详情 |