(E)-2-butenenitrile -Drug Synthesis Database

【结构式】

【分子编号】24144

【品名】(E)-2-butenenitrile

【CA登记号】4786-20-3

【分子式】C₄H₅N

【分子量】67.09044

【元素组成】C 71.61% H 7.51% N 20.88%

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：(III)

The reaction of 4-bromo-2-thiophienecarboxaldehyde (I) with imidazole yields 4-(1H-imidazol-1-yl)-2 thiophenecarboxaldehyde (II), which by cyanide-catalyzed conjugate addition to 2-butenenitrile (III) in DMF is converted to 4-[4-(1H-imidazol-1-yl)-2-thienyl]-3-methyl-4-oxobutyronitrile (IV). Hydrolysis of (IV) in refluxing 4N HCl gives 4-[4-(1H imidazol-1-yl)-2-thienyl-4 oxobutanoic acid (V), which is finally cyclized with hydrazine in refluxing water to afford motapizone.

参考文献中间体

合成目标

【1】 Borbe, H.; Doppelfeld, I.-S.; Hilboll, G.; Lohr, J.P.; Prop, G. (A. Nattermann & Cie. GmbH); Imidazolylalkylthienyl tetrahydropyridazines and processes for their use. DE 3241102; EP 0112987; US 4644998 .
【2】 Prop, G.; Hilboll, G.; Borbe, H.O.; Motapizone. Drugs Fut 1986, 11, 1, 24.

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)	24142	4-bromo-2-thiophenecarbaldehyde	18791-75-8	C₅H₃BrOS	详情	详情
(II)	24143	4-(1H-Imidazol-1-yl)-2-thiophenecarbaldehyde; 4-(1H-Imidazol-1-yl)-2 thiophenecarboxaldehyde		C₈H₆N₂OS	详情	详情
(III)	24144	(E)-2-butenenitrile	4786-20-3	C₄H₅N	详情	详情
(IV)	24145	4-[4-(1H-imidazol-1-yl)-2-thienyl]-3-methyl-4-oxobutanenitrile		C₁₂H₁₁N₃OS	详情	详情
(V)	24146	4-[4-(1H-imidazol-1-yl)-2-thienyl]-3-methyl-4-oxobutyric acid		C₁₂H₁₂N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The reaction of 4-(1H-imidazol-1-yl)benzaldehyde (I) with morpholine (A) and KCN in dioxane water by means of p-toluenesulfonic acid gives [4-(1H-imidazol-1-yl)phenyl](4morpholinyl)acetonitrile (II), which is condensed with crotononitrile (III) by means of KOH in methanol yielding 4-[4-(1H-imidazol-1-yl)phenyl]-3-methyl-4-oxobutyronitrile (IV). The hydrolysis of (IV) with hot aqueous HCl affords 4-[4-(1H-imidazol-1-yl)phenyl]-3-methyl-4-oxobutanoic acid (V), which is finally cyclized with hydrazine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Guengerich, F.P.; Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)pyridazinones: Novel positive inotropic agents for the treatment of congestive heart failure. J Med Chem 1984, 27, 9, 1099.
【2】 Sircar, I.; Bristol, J.A. (Pfizer Inc.); Substituted 4,5-dihydro-6-(substituted)phenyl-3(2H)-pyridazinones and 6-(substituted)phenyl-3(2H)-pyridazinones. CA 1190548; DD 208615; EP 0075436 .
【3】 Castaner, J.; Serradell, M.N.; CI-930. Drugs Fut 1985, 10, 6, 449.

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)	29649	4-(1H-imidazol-1-yl)benzaldehyde	10040-98-9	C₁₀H₈N₂O	详情	详情
(II)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(III)	29650	2-[4-(1H-imidazol-1-yl)phenyl]-2-(4-morpholinyl)acetonitrile		C₁₅H₁₆N₄O	详情	详情
(IV)	24144	(E)-2-butenenitrile	4786-20-3	C₄H₅N	详情	详情
(V)	29651	4-[4-(1H-imidazol-1-yl)phenyl]-3-methyl-4-oxobutanenitrile		C₁₄H₁₃N₃O	详情	详情
(VI)	29652	4-[4-(1H-imidazol-1-yl)phenyl]-3-methyl-4-oxobutyric acid		C₁₄H₁₄N₂O₃	详情	详情

Extended Information