【结 构 式】 |
【分子编号】15356 【品名】(5S)-5-[[3-(2-aminoethyl)-1H-indol-5-yl]methyl]-1H-imidazole-2,4(3H,5H)-dione 【CA登记号】 |
【 分 子 式 】C14H16N4O2 【 分 子 量 】272.3068 【元素组成】C 61.75% H 5.92% N 20.57% O 11.75% |
合成路线1
该中间体在本合成路线中的序号:(XVII)6) The cyclization of L-4-nitrophenylalanine (I) with benzyl isocyanate (XIII) in hot water gives (S)-5-(4-nitrobenzyl)imidazolidine-2,4-dione (XIV), which is reduced with H2 over Pd/C in ethanol/water to the corresponding amino derivative (XV). The diazotation of (XV) with NaNO2.HCl, followed by reduction with SnCl2 in water affords the expected hydrazino derivative (XVI), which is cyclized with 4-chlorobutanal diethylacetal (VII) in refluxing ethanol/water to give (S)-5-[3-(2-aminoethyl)-1H-indol-5-ylmethyl]imidazolidine-2,4-dione (XVII). The reductive methylation of (XVII) with formaldehyde and sodium cyanoborohydride yields (S)-5-[3-[2-(dimethylamino)ethyl]-1H-indol-3-yl]alanine (XIX). The esterification of (XIX) with SOCl2 and methanol affords the corresponding methyl ester (XX), which is reduced with NaBH4 in ethanol/water giving the 2(S)-aminopropanol derivative (XXI). Finally, this compound is cyclized with diethyl carbonate and potassium carbonate at 130 C. 7) The cyclization of hydrazino derivative (XVI) with 4-(dimethylamino)butanal diethylacetal (IX) in refluxing acetic acid/water directly yields (S)-5-[3-[2-(dimethylamino)ethyl]-1H-indol-5-ylmethyl]imidazolidine-2,4-dione (XVIII), already reported.
【1】 Ngo, J.; Mealy, N.; Castaner, J.; Zolmitriptan. Drugs Fut 1997, 22, 3, 260. |
【2】 Robertson, A.D.; Hill, A.P.; Glen, R.C.; Martin, G.R. (Glaxo Wellcome plc); Therapeutic heterocyclic cpds.. EP 0486666; EP 0636623; JP 1993502679; US 5399574; US 5466699; WO 9118897 . |
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) | 15341 | (2S)-2-amino-3-(4-nitrophenyl)propionic acid; 4-nitro-L-phenylalanine | 949-99-5 | C9H10N2O4 | 详情 | 详情 |
(VII) | 15347 | 4-Chloro-1-ethoxybutyl ethyl ether; 4-Chloro-1,1-diethoxybutane; 4-Chlorobutyraldehyde diethyl acetal | 6139-83-9 | C8H17ClO2 | 详情 | 详情 |
(IX) | 15349 | N-(4,4-diethoxybutyl)-N,N-dimethylamine; 4,4-diethoxy-N,N-dimethyl-1-butanamine | C10H23NO2 | 详情 | 详情 | |
(XIV) | 15353 | (5S)-5-(4-nitrobenzyl)-1H-imidazole-2,4(3H,5H)-dione | C10H9N3O4 | 详情 | 详情 | |
(XV) | 15354 | (5S)-5-(4-aminobenzyl)-1H-imidazole-2,4(3H,5H)-dione | C10H11N3O2 | 详情 | 详情 | |
(XVI) | 15355 | (5S)-5-(4-hydrazinobenzyl)-1H-imidazole-2,4(3H,5H)-dione | C10H12N4O2 | 详情 | 详情 | |
(XVII) | 15356 | (5S)-5-[[3-(2-aminoethyl)-1H-indol-5-yl]methyl]-1H-imidazole-2,4(3H,5H)-dione | C14H16N4O2 | 详情 | 详情 | |
(XVIII) | 15357 | (5S)-5-([3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl)-1H-imidazole-2,4(3H,5H)-dione | C16H20N4O2 | 详情 | 详情 | |
(XIX) | 15358 | (2S)-2-amino-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]propionic acid | C15H21N3O2 | 详情 | 详情 | |
(XX) | 15359 | methyl (2S)-2-amino-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]propanoate | C16H23N3O2 | 详情 | 详情 | |
(XXI) | 15360 | (2S)-2-amino-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-1-propanol | C15H23N3O | 详情 | 详情 |