-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】1-[3-(Trifluoromethyl)phenyl]-4-[2-[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethylperhydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepin-10-yl]ethyl]piperazine
　　　　　　10(R)-[2-[4-[3-(Trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-10-deoxoartemisinin

【CA登记号】

【分子式】C₂₈H₃₉F₃N₂O₄

【分子量】524.62923

【开发单位】University of Liverpool (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Treatment of Protozoal Diseases

合成路线1

The reaction of dihydroartemisinin (I) with benzoyl chloride in pyridine gives the benzoate (II), which is treated with alyltrimethylsilane (III) and ZnCl2 in dichloroethane to yield the allyl-artemisinin derivative (IV). The ozonolysis of the vinyl group of (IV), followed by reduction with NaBH4, affords the 2-hydroxyethyl derivative (V). The reaction of (V) with Ms-Cl and TEA provides the mesylate (VI), which is finally condensed with 1-[3-(trifluoromethyl)phenyl]piperazine (VII) in refluxing benzene to furnish the target piperazinylethyl derivative.

参考文献中间体

【1】 Hindley, S.; Bray, P.G.; Ward, S.A.; Searle, N.L.; Park, B.K.; Davies, J.; O'Neill, P.M.; Storr, R.C.; Mechanism-based design of parasite-targeted artemisinin derivatives: Synthesis and antimalarial activity of new diamine containing analogues. J Med Chem 2002, 45, 5, 1052.

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)	54785	(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9,12-tetramethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecan-10-ol		C₁₆H₂₆O₅	详情	详情
(II)	54786	(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9,12-tetramethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl benzoate		C₂₃H₃₀O₆	详情	详情
(III)	15775	Allyltrimethylsilane; allyl(trimethyl)silane	762-72-1	C₆H₁₄Si	详情	详情
(IV)	54787	(1R,4S,5R,8S,9R,10R,12R,13R)-10-allyl-1,5,9,12-tetramethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane		C₁₉H₃₀O₄	详情	详情
(V)	54788	2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9,12-tetramethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]-1-ethanol		C₁₈H₃₀O₅	详情	详情
(VI)	54789	2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9,12-tetramethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]ethyl methanesulfonate		C₁₉H₃₂O₇S	详情	详情
(VII)	16172	1-[3-(trifluoromethyl)phenyl]piperazine; N-[3-(trifluoromethyl)phenyl]piperazine	15532-75-9	C₁₁H₁₃F₃N₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)