2-(methylsulfanyl)-1H-pyrrole -Drug Synthesis Database

【结构式】

【分子编号】24831

【品名】2-(methylsulfanyl)-1H-pyrrole

【CA登记号】

【分子式】C₅H₇NS

【分子量】113.18332

【元素组成】C 53.06% H 6.23% N 12.38% S 28.33%

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：(II)

This compound can be obtained in the following way: 1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III), which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV). The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI), which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII). The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII), which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.

参考文献中间体

合成目标

【1】 Greenhouse, R.; Franco, F.; Novel syntheses of 5-aroyl-1,2-dihydro-3H-pyrrole-1-carboxilic acids. J Org Chem 1982, 47, 1682.
【2】 Engler, H.; Schickaneder, H.; Szelenyi, I. (Heumann Pharma GmbH & Co.); Imidazoyl-substd. thiomethylpyridine derivs., method of administration thereof and medicaments containing them. DE 3216843; EP 0093252; US 4810715 .
【3】 Muchowski, J.M.; Greenhouse, R. (Roche Bioscience); Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein. US 4347186 .
【4】 Prous, J.; Castaner, J.; Anirolac. Drugs Fut 1986, 11, 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)	24830	4-methoxy-N,N-dimethylbenzamide		C₁₀H₁₃NO₂	详情	详情
(II)	24831	2-(methylsulfanyl)-1H-pyrrole		C₅H₇NS	详情	详情
(III)	24832	(4-methoxyphenyl)[5-(methylsulfanyl)-1H-pyrrol-2-yl]methanone		C₁₃H₁₃NO₂S	详情	详情
(IV)	24833	(4-methoxyphenyl)[5-(methylsulfonyl)-1H-pyrrol-2-yl]methanone		C₁₃H₁₃NO₄S	详情	详情
(V)	11639	6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione	5617-70-9	C₈H₁₀O₄	详情	详情
(VI)	24835	5-[2-[2-(4-methoxybenzoyl)-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₂₁H₂₃NO₈S	详情	详情
(VII)	24836	dimethyl 2-[2-[2-(4-methoxybenzoyl)-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]malonate		C₂₀H₂₃NO₈S	详情	详情
(VIII)	24837	dimethyl 5-(4-methoxybenzoyl)-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylate		C₁₉H₁₉NO₆	详情	详情
(XI)	24838	5-[2-[2-(4-methoxybenzoyl)-5-(methylsulfanyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₂₁H₂₃NO₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The benzoylation of 2-methylthiopyrrole (I) with N,N-dimethylbenzamide (II) by means of POCl3 in refluxing CH2Cl2 gives 5-benzoyl-2-methylthiopyrrole (III), which is condensed with spiro[2.5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione (IV) by means of NaH in DMF yielding compound (V). The oxidation of (V) with m-chloroperbenzoic acid in CH2Cl2 affords the sulfone (VI), which is submitted to methanolysis with methanol and HCl giving 1-(3,3-dimethoxycarbonylpropyl)-2-methanesulfonyl-5-benzoylpyrrole (VII). The cyclization of (VII) with NaH in DMF yields dimethyl 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII), which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol. Compound (III) can be oxidized with m-chloroperbenzoic acid as before giving 2-methanesulfonyl-5-benzoylpyrrole (IX), which is then condensed with spiro compound (IV) as before to afford compound (VI), already obtained.

参考文献中间体

合成目标

【1】 Muchowski, J.M.; Franco, F.; Greenhouse, R.; Novel syntheses of 5-aryl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids. J Org Chem 1982, 47, 9, 1682-88.
【2】 Arrigoni-Martelli, E.; Castaner, J.; Blancafort, P.; Serradell, M.N.; RS-37,619. Drugs Fut 1983, 8, 10, 871.

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)	24831	2-(methylsulfanyl)-1H-pyrrole		C₅H₇NS	详情	详情
(II)	30757	N,N-dimethylbenzamide	611-74-5	C₉H₁₁NO	详情	详情
(III)	30758	[5-(methylsulfanyl)-1H-pyrrol-2-yl](phenyl)methanone		C₁₂H₁₁NOS	详情	详情
(IV)	11639	6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione	5617-70-9	C₈H₁₀O₄	详情	详情
(V)	30759	5-[2-[2-benzoyl-5-(methylsulfanyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₂₀H₂₁NO₅S	详情	详情
(VI)	30760	5-[2-[2-benzoyl-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₂₀H₂₁NO₇S	详情	详情
(VII)	30761	dimethyl 2-[2-[2-benzoyl-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]malonate		C₁₉H₂₁NO₇S	详情	详情
(VIII)	30762	dimethyl 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylate		C₁₈H₁₇NO₅	详情	详情
(IX)	30763	[5-(methylsulfonyl)-1H-pyrrol-2-yl](phenyl)methanone		C₁₂H₁₁NO₃S	详情	详情

Extended Information