Ivarimod, Ru-18492, -Drug Synthesis Database

【结构式】

【药物名称】Ivarimod, Ru-18492

【化学名称】N-(2-Hydroxyethyl)maleopimarimidyl morpholide
　　　　　　4-[[(3aR,3bS,5aR,6R,9aR,9bR,11R,11aR)-1,2,3,3a,4,5,,5a,6,7,8,9,9a,9b,10,11,11a-Hexadecahydro-2-(2-hydroxyethyl)-12-isopropyl-6,9a-dimethyl-1,3-dioxo-3b,11-etheno-3bH-naphth[2,1-e]isoindol-6-yl]carbonyl]morpholine

【CA登记号】53003-81-9

【分子式】C₃₀H₄₄N₂O₅

【分子量】512.69558

【开发单位】Aventis Pharma (Originator)

【药理作用】GASTROINTESTINAL DRUGS, Hepatoprotectants, IMMUNOMODULATING AGENTS, Immunomodulators, Liver and Biliary Tract Disorders, Treatment of

合成路线1 合成路线2

合成路线1

The reaction of maleopimaric acid (I) with aqueous ammonia and heating at 170 C gives maleopimarimide (II), which by reaction with oxalyl chloride in benzene is converted into the corresponding acyl chloride (III). The reaction of (III) with morpholine (A) in benzene yields maleopimarimidyl morpholide (IV), which is finally condensed with ethanolamine (B) in refluxing methanol.

参考文献中间体

【1】 Danswan, G.W.; Ramm, P.J.; Matharu, S.; Taylor, J.B.; hepatoprotective agents. II. Maleopimaridyl morpholides. Arzneim-Forsch Drug Res 1976, 26, 12, 2190-92.
【2】 Thorpe, P.; Castaner, J.; RU 18492. Drugs Fut 1977, 2, 9, 623.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(A)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(I)	40150	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-14,16-dioxo-15-oxapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-5-carboxylic acid		C₂₄H₃₂O₅	详情	详情
(II)	40151	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-14,16-dioxo-15-azapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-5-carboxylic acid		C₂₄H₃₃NO₄	详情	详情
(III)	40152	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-14,16-dioxo-15-azapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-5-carbonyl chloride		C₂₄H₃₂ClNO₃	详情	详情
(IV)	40153	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-5-(4-morpholinylcarbonyl)-15-azapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-14,16-dione		C₂₈H₄₀N₂O₄	详情	详情

合成路线2

The reaction of maleopimaric acid (I) with SOCl2 in benzene produces the corresponding acyl chloride (V), which is then condensed with morpholine (A) by means of Et3N in benzene yielding maleopimaryl morpholide (VI). Finally, (VI) is condensed with ethanolamine (B) in refluxing ethanol.

参考文献中间体

【1】 Taylor, J.B.; et al. (Aventis Pharma SA); Novel derivatives of maleopimaric acid. DE 2351343; FR 2202691; GB 1417996; JP 49093356; US 3998823 .
【2】 Thorpe, P.; Castaner, J.; RU 18492. Drugs Fut 1977, 2, 9, 623.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(A)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(I)	40150	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-14,16-dioxo-15-oxapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-5-carboxylic acid		C₂₄H₃₂O₅	详情	详情
(V)	40155	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-14,16-dioxo-15-oxapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-5-carbonyl chloride		C₂₄H₃₁ClO₄	详情	详情
(VI)	40154	(1S,4R,5R,9R,10R,12R,13R,17R)-19-isopropyl-5,9-dimethyl-5-(4-morpholinylcarbonyl)-15-oxapentacyclo[10.5.2.0(1,10).0(4,9).0(13,17)]nonadec-18-ene-14,16-dione		C₂₈H₃₉NO₅	详情	详情

Extended Information