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【结 构 式】 
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【分子编号】11279 【品名】methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate 【CA登记号】 |
【 分 子 式 】C19H22N2O2 【 分 子 量 】310.39596 【元素组成】C 73.52% H 7.14% N 9.03% O 10.31% |
合成路线1
该中间体在本合成路线中的序号：(III)The synthesis of tritiated cabergoline by two similar routes has been described: 1) The acylation of 6-nor-dihydrolysergic acid methyl ester (I) with propargyl bromide yields the corresponding 6-propargyl derivative (II), which is hydrogenated with tritium gas over Pd/C in the presence of quinoline to give the ditritiated 6-allyl derivative (III). This compound is treated with 3-(dimethylamino)propylamine at 120 C, yielding the amide (IV), which is finally treated with ethyl isocyanate. 2) The reaction of the propargyl derivative (II) with 3-(dimethylamino)propylamine as before gives the amide (V). The reaction of (V) with ethyl isocyanate gives compound (VI), which is then hydrogenated with tritium as before.
| 【1】 Mantegani, S.; Brambilla, E.; Ermoli, A.; Fontana, E.; Angiuli, P.; Vicario, G.P.; Syntheses of tritium and carbon-14 labelled N-(3-dimethyl aminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)ergoline-8beta-carboxamide (cabergoline), a potent long lasting prolactin lowering agent. J Label Compd Radiopharm 1991, 29, 5, 519. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 | |
| 28738 | ethyl isocyanate | 109-90-0 | C3H5NO | 详情 | 详情 | |
| (I) | 11273 | 8beta-Methoxycarbonylergoline; Methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate | C16H18N2O2 | 详情 | 详情 | |
| (II) | 11274 | methyl (6aR,9R,10aR)-7-(2-propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate | C19H20N2O2 | 详情 | 详情 | |
| (III) | 11279 | methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate | C19H22N2O2 | 详情 | 详情 | |
| (III) | 63076 | methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate | C19H22N2O2 | 详情 | 详情 | |
| (IV) | 11276 | (6aR,9R,10aR)-7-allyl-N-[3-(Dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide | C23H32N4O | 详情 | 详情 | |
| (IV) | 63077 | (6aR,9R,10aR)-7-allyl-N-[3-(dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide | C23H32N4O | 详情 | 详情 | |
| (V) | 11277 | (6aR,9R,10aR)-N-[3-(Dimethylamino)propyl]-7-(2-propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide | C23H30N4O | 详情 | 详情 | |
| (VI) | 11278 | N-[[(6aR,9R,10aR)-7-(2-Propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]carbonyl]-N-[3-(dimethylamino)propyl]-N'-ethylurea | C26H35N5O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The synthesis of [14C]-cabergoline has also been described: The reaction of 6-allylergoline-8beta-carboxylic acid methyl ester (I) with hydrazine in refluxing methanol gives the hydrazide (II), which by reaction with NaNO2-HCl in water is converted to the amine (III). The reaction of (III) again with NaNO2-HCl in water, followed by reaction with SnCl2, affords the chloro derivative (IV), which is condensed with [14C]-CNK in refluxing ethanol-water yielding the nitrile (V). Hydrolysis of (V) with NaOH in refluxing ethanol affords the acid (VI), which is finally condensed with N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide in DMF.
| 【1】 Mantegani, S.; Brambilla, E.; Ermoli, A.; Fontana, E.; Angiuli, P.; Vicario, G.P.; Syntheses of tritium and carbon-14 labelled N-(3-dimethyl aminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)ergoline-8beta-carboxamide (cabergoline), a potent long lasting prolactin lowering agent. J Label Compd Radiopharm 1991, 29, 5, 519. |
| 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) | 11279 | methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate | C19H22N2O2 | 详情 | 详情 | |
| (II) | 11280 | (6aR,9R,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carbohydrazide | C18H22N4O | 详情 | 详情 | |
| (III) | 11281 | (6aR,9R,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-amine; (6aR,9R,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-ylamine | C17H21N3 | 详情 | 详情 | |
| (IV) | 11282 | (6aR,9R,10aR)-7-Allyl-9-chloro-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline | C17H19ClN2 | 详情 | 详情 | |
| (V) | 11283 | (6aR,9R,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carbonitrile | C18H19N3 | 详情 | 详情 | |
| (V) | 63078 | (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carbonitrile | C18H19N3 | 详情 | 详情 | |
| (VI) | 11284 | (6aR,9R,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid | C18H20N2O2 | 详情 | 详情 | |
| (VI) | 28739 | (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid | C18H20N2O2 | 详情 | 详情 |