(6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】28739

【品名】(6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid

【CA登记号】

【分子式】C₁₈H₂₀N₂O₂

【分子量】296.36908

【元素组成】C 72.95% H 6.8% N 9.45% O 10.8%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

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.

参考文献中间体

合成目标

【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	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

合成路线2

该中间体在本合成路线中的序号：(III)

This compound can be obtained by two differents ways: 1) By condensation of 6-allyl-N-[3-(dimethylamino)propyl]ergolin-8-beta-caboxamide (I) with ethyl isocyanate (II) in refluxing toluene. 2) By condensation of 6-allylergolin-8-beta-carboxylic acid (III) with N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide (IV) in refluxing THF.

参考文献中间体

合成目标

【1】 Temperilli, A.; Bernardi, L.; Brambilla, E. (Pharmacia Corp.); Regiospecific process for the preparation of ergoline derivatives. BE 0894060; JP 58038282 .
【2】 Salvati, P.; et al. (Pharmacia & Upjohn SpA); Composés dérivés de l'ergoline, procédé pour les préparer et leur usage comme médicaments. DE 3112861; FR 2479829 .
【3】 Serradell, M.N.; Azccheo, T.; Castaner, J.; Castaner, R.M.; Giudici, D.; Cabergoline. Drugs Fut 1987, 12, 9, 842.

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)	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
(II)	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(III)	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
(IV)	24945	N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide	25952-53-8	C₈H₁₇N₃	详情	详情

Extended Information