Quinagolide hydrochloride, SDZ-205502, CV-205502, Norprolac-药物合成数据库

【药物名称】Quinagolide hydrochloride, SDZ-205502, CV-205502, Norprolac

化学结构式(Chemical Structure):

参考文献No.	250
标题:	Novel pharmaceutically active 1,2,3,4,4a,5,10,10a-octahydrobenzo(g)quinoline derivs.
作者:	Petcher, T.J.; Nordmann, R. (Novartis AG)
来源:	EP 0077754; ES 8606281; ES 8706120

合成路线图解说明: The reaction of 5-methoxy-2-tetralone (I) with benzenethiosulfonic acid S-phenyl ester and sodium acetate in methanol gives 1,1-bis(phenylsulfanyl)-2-tetralone (II), which is condensed with 2-(bromomethyl)acrylic acid tert-butyl ester (III) by means of n-BuLi and diisopropylamine (DIA) in THF to yield the acrylic acid derivative (IV). Desulfurization of (IV) with Al/Hg in THF/water affords compound (V), which is treated with O-methylhydroxylamine and Na2HPO4 in methanol, providing the methoxyimino compound (VI). The reduction of (VI) with Zn/HOAc provides the methoxyamino compound (VII). The cyclization of (VII) by means of potassium hydrogen phosphate gives 1,6-dimethoxy-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-3-carboxylic acid tert-butyl ester as a diastereomeric mixture that is separated by chromatography to furnish the desired diastereomer (VIII). Hydrolysis of the tert-butoxy ester group of (VIII) by means of TFA yields the carboxylic acid (IX), which is treated with diazomethane to afford the methyl ester (X). Selective demethoxylation of (X) with Zn/HOAc provides the octahydrobenzoquinoline (XI).

合成路线图解说明: Free NH group of (XI) is alkylated by reductocondensation with propionaldehyde (XII) and H2 over Pd/C, giving the N-propyl derivative (XIII). The reaction of the ester group of (XIII) with hydrazine yields the corresponding hydrazide (XIV), which is submitted to degradation with nitrosyl chloride in THF to afford the amine (XV). The condensation of (XV) with N,N-diethylsulfamoyl chloride (XVI) by means of TEA in chloroform gives the sulfamide (XVII), which is finally demethylated by a treatment with BBr3 in dichloromethane.

参考文献No.	608393
标题:	Octahydrobenzo[g]quinolines: Potent dopamine agonists which show the relationship between ergolines and apomorphine
作者:	Nordmann, R.; Petcher, T.J.
来源:	J Med Chem 1985,28(3),367

合成路线图解说明: The reaction of 5-methoxy-2-tetralone (I) with benzenethiosulfonic acid S-phenyl ester and sodium acetate in methanol gives 1,1-bis(phenylsulfanyl)-2-tetralone (II), which is condensed with 2-(bromomethyl)acrylic acid tert-butyl ester (III) by means of n-BuLi and diisopropylamine (DIA) in THF to yield the acrylic acid derivative (IV). Desulfurization of (IV) with Al/Hg in THF/water affords compound (V), which is treated with O-methylhydroxylamine and Na2HPO4 in methanol, providing the methoxyimino compound (VI). The reduction of (VI) with Zn/HOAc provides the methoxyamino compound (VII). The cyclization of (VII) by means of potassium hydrogen phosphate gives 1,6-dimethoxy-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-3-carboxylic acid tert-butyl ester as a diastereomeric mixture that is separated by chromatography to furnish the desired diastereomer (VIII). Hydrolysis of the tert-butoxy ester group of (VIII) by means of TFA yields the carboxylic acid (IX), which is treated with diazomethane to afford the methyl ester (X). Selective demethoxylation of (X) with Zn/HOAc provides the octahydrobenzoquinoline (XI).

合成路线图解说明: Free NH group of (XI) is alkylated by reductocondensation with propionaldehyde (XII) and H2 over Pd/C, giving the N-propyl derivative (XIII). The reaction of the ester group of (XIII) with hydrazine yields the corresponding hydrazide (XIV), which is submitted to degradation with nitrosyl chloride in THF to afford the amine (XV). The condensation of (XV) with N,N-diethylsulfamoyl chloride (XVI) by means of TEA in chloroform gives the sulfamide (XVII), which is finally demethylated by a treatment with BBr3 in dichloromethane.