N,N-dimethylbenzamide -Drug Synthesis Database

【结构式】

【分子编号】30757

【品名】N,N-dimethylbenzamide

【CA登记号】611-74-5

【分子式】C₉H₁₁NO

【分子量】149.19248

【元素组成】C 72.46% H 7.43% N 9.39% O 10.72%

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)

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

合成路线2

该中间体在本合成路线中的序号：(XXII)

The condensation of dimethylacetone-1,3-dicarboxylate (X) with ethanolamine (XI) yields methyl 3-(methoxycarbonylmethyl)-3-(2-hydroxyethylamino)acrylate (XII), which is cyclized with bromoacetaldehyde diethylacetal (XIII) affording methyl 1-(2-hydroxyethyl)-3-methoxycarbonylpyrrol-2-acetate (XIV). Acylation of (XIV) with methanesulfonyl chloride (XV) and triethylamine in CH2Cl2 yields the corresponding mesylate (XVI), which by treatment with methyl iodide in refluxing acetonitrile is converted into methyl 1-(2-iodoethyl)-3-methoxycarbonylpyrrole-2-acetate (XVII). The cyclization of (XVII) with NaH in DMF yields dimethyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylate (XVIII), which is hydrolyzed with KOH in refluxing methanol - water to the corresponding diacid (XIX). Partial esterification of (XIX) with isopropanol and HCl gives isopropyl 1,2-dihydro-3H-7-carboxypyrrolo[1,2-a]pyrrole-1-carboxylate (XX), which is decarboxylated by heating at 270 C affording isopropyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate (XXI). Benzoylation of (XXI) with N,N-dimethylbenzamide (XXII) and POCl3 in refluxing CH2Cl2 yields isopropyl 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate (XXIII), which is finally hydrolyzed with K2CO3 or NaOH in methanol - water.

参考文献中间体

合成目标

【1】 Blancafort, P.; Serradell, M.N.; Hillier, K.; Castaner, J.; BPPC. Drugs Fut 1981, 6, 11, 669.
【2】 Muchowski, J.M.; Kluge, A.F. (Roche Bioscience); 1,2-Dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids derivatives and process for the production thereof. DE 2731678; ES 460706; ES 470214; FR 2358406; FR 2375234; GB 1554075 .
【3】 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
(X)	22692	dimethyl 3-oxopentanedioate	1830-54-2	C₇H₁₀O₅	详情	详情
(XI)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(XII)	30764	dimethyl (E)-3-[(2-hydroxyethyl)amino]-2-pentenedioate		C₉H₁₅NO₅	详情	详情
(XIII)	12113	2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal	2032-35-1	C₆H₁₃BrO₂	详情	详情
(XIV)	30765	methyl 1-(2-hydroxyethyl)-2-(2-methoxy-2-oxoethyl)-1H-pyrrole-3-carboxylate		C₁₁H₁₅NO₅	详情	详情
(XVI)	30766	methyl 2-(2-methoxy-2-oxoethyl)-1-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl)-1H-pyrrole-3-carboxylate		C₁₄H₂₁NO₅S	详情	详情
(XVII)	30767	methyl 1-(2-iodoethyl)-2-(2-methoxy-2-oxoethyl)-1H-pyrrole-3-carboxylate		C₁₁H₁₄INO₄	详情	详情
(XVIII)	30768	dimethyl 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylate		C₁₁H₁₃NO₄	详情	详情
(XIX)	30769	2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylic acid		C₉H₉NO₄	详情	详情
(XX)	30770	1-(isopropoxycarbonyl)-2,3-dihydro-1H-pyrrolizine-7-carboxylic acid		C₁₂H₁₅NO₄	详情	详情
(XXI)	30771	isopropyl 2,3-dihydro-1H-pyrrolizine-1-carboxylate		C₁₁H₁₅NO₂	详情	详情
(XXII)	30757	N,N-dimethylbenzamide	611-74-5	C₉H₁₁NO	详情	详情
(XXIII)	30772	isopropyl 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylate		C₁₈H₁₉NO₃	详情	详情

Extended Information