【结 构 式】 |
【药物名称】Pazinaclone, A-77000, DN-2327 【化学名称】(±)-2-(7-Chloro-1,8-naphthyridin-2-yl)-3-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxoethyl]isoindolin-1-one 【CA登记号】103255-66-9 【 分 子 式 】C25H23ClN4O4 【 分 子 量 】478.93946 |
【开发单位】Takeda (Originator), TAP (Originator) 【药理作用】Anxiolytics, PSYCHOPHARMACOLOGIC DRUGS, GABA(A) BZ Site Receptor Partial Agonists |
合成路线1
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 |