|
【结 构 式】 
|
【分子编号】49143 【品名】(3S)-4-[benzoyl(methyl)amino]-3-(3,4-dichlorophenyl)butyl benzenesulfonate 【CA登记号】 |
【 分 子 式 】C24H23Cl2NO4S 【 分 子 量 】492.42236 【元素组成】C 58.54% H 4.71% Cl 14.4% N 2.84% O 13% S 6.51% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)In a further method, the chiral amino alcohol (IX) was acylated with benzoyl chloride to afford the benzamide (XXVII). Subsequent protection of the hydroxyl group of (XXVII) with dihydropyran provided the tetrahydropyranyl ether (XXVIII). Alternatively, amino alcohol (IX) was initially protected as the tetrahydropyranyl derivative (XXIX), which was subsequently acylated with benzoyl chloride . N-Alkylation of amide (XXVIII) to give (XXX) was either performed with dimethyl sulfate or with methyl iodide in the presence of NaH. Subsequent deprotection of the tetrahydropyranyl ether (XXX) in acidic medium furnished alcohol (XII). This was converted to the sulfonate ester (XXXI) upon treatment with benzenesulfonyl chloride and Et3N. Alternatively, alcohol (XII) was converted to the corresponding mesylate as shown in Scheme 1 (5). Finally, condensation of the benzenesulfonate (XXXI) with piperidine (III) in the presence of K2CO3 in refluxing acetonitrile yielded the title compound
| 【1】 Descamps, M.; Radisson, J.; Anne-Archard, G. (Sanofi-Synthélabo); Process for the preparation of the (-)-N-methyl-N-[4-(4-phenyl-4-acetyl-aminopiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-benzamide and its pharmaceutically acceptable salts. EP 0698601 . |
| 【2】 Emonds-Alt, X.; Proietto, V.; Van Broeck, D.; Vilain, P.; Advenier, C.; Neliat, G.; Le Fur, G.; Breliere, J.-C.; Pharmacological profile and chemical synthesis of SR 48968, a non-peptide antagonist of the neurokinin A (NK2) receptor. Bioorg Med Chem Lett 1993, 3, 5, 925. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 59283 | N-(4-phenyl-4-piperidinyl)acetamide | C13H18N2O | 详情 | 详情 | |
| (IX) | 26939 | (3S)-4-amino-3-(3,4-dichlorophenyl)-1-butanol | C10H13Cl2NO | 详情 | 详情 | |
| (XII) | 26942 | N-[(2S)-2-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methylbenzamide | C18H19Cl2NO2 | 详情 | 详情 | |
| (XXVII) | 62388 | N-[(2S)-2-(3,4-dichlorophenyl)-4-hydroxybutyl]benzamide | C17H17Cl2NO2 | 详情 | 详情 | |
| (XXVIII) | 62389 | N-[(2S)-2-(3,4-dichlorophenyl)-4-(tetrahydro-2H-pyran-2-yloxy)butyl]benzamide | C22H25Cl2NO3 | 详情 | 详情 | |
| (XXIX) | 62390 | (2S)-2-(3,4-dichlorophenyl)-4-(tetrahydro-2H-pyran-2-yloxy)butylamine; (2S)-2-(3,4-dichlorophenyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butanamine | C15H21Cl2NO2 | 详情 | 详情 | |
| (XXX) | 62391 | N-[(2S)-2-(3,4-dichlorophenyl)-4-(tetrahydro-2H-pyran-2-yloxy)butyl]-N-methylbenzamide | C23H27Cl2NO3 | 详情 | 详情 | |
| (XXXI) | 49143 | (3S)-4-[benzoyl(methyl)amino]-3-(3,4-dichlorophenyl)butyl benzenesulfonate | C24H23Cl2NO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The benzonaphthyridine system (III) was prepared by condensation of 1-Boc-4-piperidone (I) with 2-aminobenzonitrile (II) in the presence of ZnCl2. After acetylation of the 10-amino group of (III) with Ac2O in pyridine to afford (IV), the N-Boc protecting group was removed by treatment with HCl in dioxan-methanol, yielding 10-acetylamino-1,2,3,4-tetrahydrobenzo[b][1,6]-naphthyridine (V). The tricyclic amine (V) was then alkylated with the chiral sulfonate (VI), and the target compound was finally converted to the corresponding fumarate salt.
| 【1】 Honda, M.; Sato, Y.; Oka, H.; Iida, M. (Nippon Kayaku Co., Ltd.); Novel naphthyridine derivs. or salts thereof. EP 0997462; JP 2000038386; US 6294547; WO 9900388 . |
| 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) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (II) | 19493 | 2-aminobenzonitrile | 1885-29-6 | C7H6N2 | 详情 | 详情 |
| (III) | 49140 | tert-butyl 10-amino-3,4-dihydrobenzo[b][1,6]naphthyridine-2(1H)-carboxylate | C17H21N3O2 | 详情 | 详情 | |
| (IV) | 49141 | tert-butyl 10-(acetamido)-3,4-dihydrobenzo[b][1,6]naphthyridine-2(1H)-carboxylate | C19H23N3O3 | 详情 | 详情 | |
| (V) | 49142 | N-(1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridin-10-yl)acetamide | C14H15N3O | 详情 | 详情 | |
| (VI) | 49143 | (3S)-4-[benzoyl(methyl)amino]-3-(3,4-dichlorophenyl)butyl benzenesulfonate | C24H23Cl2NO4S | 详情 | 详情 |