【结 构 式】 |
【药物名称】MR-18445 【化学名称】4-[4-(4-Fluorobenzyl)piperazin-1-yl]-7-methoxypyrrolo[1,2-a]quinoxaline 【CA登记号】160656-76-8, 190135-40-1 (as dihydrochloride), 212620-15-0 (labeled) 【 分 子 式 】C23H23FN4O 【 分 子 量 】390.46436 |
【开发单位】ADIR (Originator) 【药理作用】Anxiolytics, Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, 5-HT3 Agonists, 5-HT3 Antagonists |
合成路线1
Phenyl pyrrole (III) was prepared by Clauson-Kaas reaction of 4-methoxy-2-nitroaniline (I) with 2,5-dimethoxytetrahydrofuran (II). Subsequent reduction of the nitro group of (III) using hydrazine and Raney Nickel provided aniline (IV), which was cyclized with phosgene in refluxing toluene to furnish the pyrroloquinoxaline (V). This was chlorinated with POCl3 to obtain the chloroquinoxaline (VI). Finally, nucleophilic substitution in (VI) with N-(4-fluorobenzyl)piperazine (VII) yielded the title compound.
【1】 Katounina, T.; et al.; Synthesis of [18F]MR 18445 and its in vivo evaluat. J Label Compd Radiopharm 1997, 40, 542. |
【2】 Lancelot, J.-C.; Prunier, H.; Rault, S.; et al.; Novel and selective partial agonists of 5-HT3 rece. J Med Chem 1997, 40, 12, 1808. |
【3】 Katounina, T.; et al.; Synthesis and biological investigations of [18F]MR. Bioorg Med Chem 1998, 6, 6, 789. |
【4】 Rault, S.; Lancelot, J.-C.; Prunier, H.; Robba, M.; Delagrange, P.; Renard, P.; Adam, G. (ADIR et Cie.); Pyrrolopyrazine derivs. with 5-HT3 activity. CA 2122890; EP 0623620; FR 2704547; JP 1994340666; US 5599812 . |
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) | 23592 | 4-methoxy-2-nitrophenylamine; 4-methoxy-2-nitroaniline | 96-96-8 | C7H8N2O3 | 详情 | 详情 |
(II) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
(III) | 23594 | 1-(4-methoxy-2-nitrophenyl)-1H-pyrrole; methyl 3-nitro-4-(1H-pyrrol-1-yl)phenyl ether | C11H10N2O3 | 详情 | 详情 | |
(IV) | 23595 | 5-methoxy-2-(1H-pyrrol-1-yl)phenylamine; 5-methoxy-2-(1H-pyrrol-1-yl)aniline | C11H12N2O | 详情 | 详情 | |
(V) | 23596 | 7-methoxypyrrolo[1,2-a]quinoxalin-4(5H)-one | C12H10N2O2 | 详情 | 详情 | |
(VI) | 23597 | 4-chloropyrrolo[1,2-a]quinoxalin-7-yl methyl ether; 4-chloro-7-methoxypyrrolo[1,2-a]quinoxaline | C12H9ClN2O | 详情 | 详情 | |
(VII) | 23598 | 1-(4-fluorobenzyl)piperazine | C11H15FN2 | 详情 | 详情 |
合成路线2
A synthesis for the 18F-labeled compound has also been reported. The piperazinylquinoxaline (IX) was obtained from chloroquinoxaline (VI) and excess piperazine (VIII) at 160 C. This was then alkylated with 4-[18F]fluorobenzyl iodide (X) in refluxing CH2Cl2 to provide the labeled product.
【1】 Katounina, T.; et al.; Synthesis and biological investigations of [18F]MR. Bioorg Med Chem 1998, 6, 6, 789. |
【2】 Lancelot, J.-C.; Prunier, H.; Rault, S.; et al.; Novel and selective partial agonists of 5-HT3 rece. J Med Chem 1997, 40, 12, 1808. |
【3】 Katounina, T.; et al.; Synthesis of [18F]MR 18445 and its in vivo evaluat. J Label Compd Radiopharm 1997, 40, 542. |
【4】 Rault, S.; Lancelot, J.-C.; Prunier, H.; Robba, M.; Delagrange, P.; Renard, P.; Adam, G. (ADIR et Cie.); Pyrrolopyrazine derivs. with 5-HT3 activity. CA 2122890; EP 0623620; FR 2704547; JP 1994340666; US 5599812 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 23597 | 4-chloropyrrolo[1,2-a]quinoxalin-7-yl methyl ether; 4-chloro-7-methoxypyrrolo[1,2-a]quinoxaline | C12H9ClN2O | 详情 | 详情 | |
(VIII) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
(IX) | 23600 | 7-methoxy-4-(1-piperazinyl)pyrrolo[1,2-a]quinoxaline; methyl 4-(1-piperazinyl)pyrrolo[1,2-a]quinoxalin-7-yl ether | C16H18N4O | 详情 | 详情 | |
(X) | 23601 | 1-fluoro-4-(iodomethyl)benzene | C7H6FI | 详情 | 详情 | |
(X) | 45316 | 1-fluoro-4-(iodomethyl)benzene | C7H6FI | 详情 | 详情 |