Zomepirac sodium, McN-2783-21-98, Zomax, -Drug Synthesis Database

【结构式】

【药物名称】Zomepirac sodium, McN-2783-21-98, Zomax

【化学名称】5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetic acid sodium salt dihydrate

【CA登记号】64092-49-5, 64092-48-4 (anhydrous), 33369-31-2 (free base, anhydrous)

【分子式】C₁₅H₁₇ClNNaO₅

【分子量】349.74924

【开发单位】Cilag (Originator)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Non-Steroidal Antiinflammatory Drugs

合成路线1 合成路线2

合成路线1

The hydrolysis of ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) with refluxing aqueous NaOH gives 3-carboxy-1,4-dimethylpyrrole-2-acetic acid (II), which is partially esterified with refluxing ethanol - dry HCl yielding ethyl 3-carboxy-1,4-dimethylpyrrole-2-acetate (III). The decarboxylation of (III) by heating at 190-210 C affords ethyl 1,4-dimethylpyrrole-2-acetate (IV), which by a Vilsmeier aroylation with p-chloro-N,N-dimethylbenzamide (A) and POCl3 in refluxing dichloroethane is converted into ethyl 5-p-chlorobenzoyl-1,4-dimethylpyrrole-2-acetate (V). Finally, this product is hydrolyzed with refluxing aqueous 1N NaOH.

参考文献中间体

【1】 Hillier, K.; Castañer, J.; Zomepirac. Drugs Fut 1977, 2, 10, 698.
【2】 Wong, S.; Carson, J.R.; 5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents. 2. The 4-methyl compounds. J Med Chem 1973, 16, 2, 172-174.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	40139	4-chloro-N,N-dimethylbenzamide	14062-80-7	C₉H₁₀ClNO	详情	详情
(I)	40135	ethyl 2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylate		C₁₃H₁₉NO₄	详情	详情
(II)	40136	2-(carboxymethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid	33369-45-8	C₉H₁₁NO₄	详情	详情
(III)	40137	2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid		C₁₁H₁₅NO₄	详情	详情
(IV)	40138	ethyl 2-(1,4-dimethyl-1H-pyrrol-2-yl)acetate		C₁₀H₁₅NO₂	详情	详情
(V)	40140	ethyl 2-[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]acetate		C₁₇H₁₈ClNO₃	详情	详情

合成路线2

The starting product ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) can be obtained by condensation of diethyl acetonedicarboxylate (X) with chloroacetone (IX) by means of methylamine in water, the compound (XI) being formed as an intermediate which is not isolated. The Friedel-Crafts aroylation of (I) with p-chlorobenzoyl chloride (B) and AlCl3 in refluxing dichloroethane gives ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (VI), which by hydrolysis with aqueous 1N NaOH yields 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetic acid (VII). The partial esterification of (VII) with ethanol and HCl produces ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetate (VIII), which by decarboxylation at 210-30 C is converted into the ester (V) already obtained.

参考文献中间体

【1】 Carson, J.R.; Aroyl-substituted pyrroles. DE 2102746; FR 2081455; GB 1327308; JP 55033401; JP 55033402; US 3752826; US 3865840; US 4070368 .
【2】 Hillier, K.; Castañer, J.; Zomepirac. Drugs Fut 1977, 2, 10, 698.

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)	10295	p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride	122-01-0	C₇H₄Cl₂O	详情	详情
(I)	40135	ethyl 2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylate		C₁₃H₁₉NO₄	详情	详情
(V)	40140	ethyl 2-[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]acetate		C₁₇H₁₈ClNO₃	详情	详情
(VI)	40143	ethyl 5-(4-chlorobenzoyl)-2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylate		C₂₀H₂₂ClNO₅	详情	详情
(VII)	40144	2-(carboxymethyl)-5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid		C₁₆H₁₄ClNO₅	详情	详情
(VIII)	40145	5-(4-chlorobenzoyl)-2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid		C₁₈H₁₈ClNO₅	详情	详情
(IX)	15288	1-Chloroacetone; Chloroacetone	78-95-5	C₃H₅ClO	详情	详情
(X)	40141	diethyl 3-oxopentanedioate	105-50-0	C₉H₁₄O₅	详情	详情
(XI)	40142	methanaminium 1-chloro-6-ethoxy-3-(ethoxycarbonyl)-2-methyl-4,6-dioxo-2-hexanolate		C₁₃H₂₄ClNO₆	详情	详情

Extended Information