|
【结 构 式】 
|
【药物名称】T-82 【化学名称】2-[2-(1-Benzylpiperidin-4-yl)ethyl]-9-methoxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate 【CA登记号】142471-56-5 (free base) 【 分 子 式 】C30H33N3O6 【 分 子 量 】531.61401 |
【开发单位】SSP (Originator), Arena (Licensee) 【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, 5-HT3 Antagonists, Acetylcholinesterase Inhibitors |
合成路线1
The reaction of methyl anthranilate (I) with tetrahydrofuran-2,4-dione (II) by means of HCl in ethanol gives 2-(5-oxo-2,5-dihydrofuran-3-ylamino)benzoic acid methyl ester (III), which is cyclized by means of polyphosphoric acid (PPA) at 130-140 C yielding the tricyclic hydroxyketone (IV). The condensation of (IV) with 4-(2-aminoethyl)-1-benzylpiperidine (V) in N-methyl-2-pyrrolidone by a Dean-Stark elimination of water affords 2-[2-(1-benzyl-piperidin-4-yl)ethyl]-9-hydroxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one (VI), which is finally methylated with diazomethane in methanol.
| 【1】 Castañer, J.; Mucke, H.A.M.; T-82. Drugs Fut 1998, 23, 10, 1075-1077. |
| 【2】 Hasegawa, H.; Isomae, K.; Kotsugai, T.; Shioiri, N.; Sekine, K.; Taido, N.; Sato, S.; Kuraishi, T. (SSP Co., Ltd.); Quinoline derivs.. EP 0481429; JP 1993009188; JP 1993279355; US 5190951; US 5240934; US 5300517 . |
| 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) | 11161 | methyl 2-aminobenzoate; Methyl anthranilate | 134-20-3 | C8H9NO2 | 详情 | 详情 |
| (II) | 17603 | Tetronic acid; 2,4(3H,5H)-Furandione | 4971-56-6 | C4H4O3 | 详情 | 详情 |
| (III) | 17604 | methyl 2-[(5-oxo-2,5-dihydro-3-furanyl)amino]benzoate | C12H11NO4 | 详情 | 详情 | |
| (IV) | 17605 | 9-hydroxyfuro[3,4-b]quinolin-1(3H)-one | C11H7NO3 | 详情 | 详情 | |
| (V) | 17606 | 2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine | C14H22N2 | 详情 | 详情 | |
| (VI) | 17607 | 2-[2-(1-benzyl-4-piperidinyl)ethyl]-9-hydroxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one | C25H27N3O2 | 详情 | 详情 |