Pirprofen, SU-21524, Rengasil
吡咯布洛芬Chemical Name: 3-Chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)-alpha-methylbenzeneacetic acid; 3-Chloro-4-(3-pyrrolin-1-yl)hydratropic acid
CAS No. 31793-07-4
项目整合开发状态: Launched-1982
项目研究机构: Novartis (Originator)
合成路线:The methylation of ethyl 4-nitrophenylacetate (I) with NaH - ICH3 in DMF - toluene to ethyl 2-(4-nitrophenyl)propionate (II),which was reduced with H2 over Pd/C in EtOH - H2O to ethyl 2-(4-aminophenyl)propionate (III) (HCl deriv.,m.p.137-40 C).This product was acetylated with acetic anhydride to ethyl 2-(acetylaminophenyl) propionate (IV),m.p.88-90 C,which was chlorinated with Cl2 in acetic acid to ethyl 2-(3-chloro-4-acetylaminophenyl)propionate (V),b.p.155-60 C/0.7 mm; this,in turn,was hydrolyzed with HCl in EtOH to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI),m.p.164-8 C.The last step being the reaction of the preceding intermediate with cis-1,4-dichloro (or dibromo)-2-butene (A) in DMF and Na2CO3 to ethyl 2-(3-chloro-4-(3-pyrrolinyl)phenyl)propionate (VII),b.p.128-33 C/0.25 mm; followed by hydrolysis with KOH in EtOH - H2O.The acetylation of ethyl 4-aminophenylacetate (VIII) with acetic anhydride to ethyl 4-acetylaminophenylacetate (IX),m.p.75-8 C,followed by methylation with ICH3 and Na in liquid NH3 to ethyl 2-(4-acetylaminophenyl)propionate (IV),already obtained.
合成路线:The reaction of 2,4-dichloronitrobenzene (X) with sodium diethyl methylmalonate (B) in DMF to diethyl 2-(4-nitro-3-chlorophenyl)-2-methyl-malonate (XI),b.p.147-8 C/0.25 mm,followed hydrolysis,decarboxylation and esterification to ethyl 2-(3-chloro-4-nitrophenyl)propionate (XII),b.p.138-42 C /0.25 mm; which,in turn,was reduced as before to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI).Conversely,the diethyl 2-(4-nitro-3-chlorophenyl)-2-methylmalonate (XI),already obtained before,could be hydrogenated first to diethyl 2-(4-amino-3-chlorophenyl)-2-methylmalonate (XIII),b.p.180-5 C/0.25 mm,and then hydrolyzed,decarboxylated and esterified again to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI).
📌 参考资料/链接：
参考文献标题:Pirprofen
文献作者:Castar,J.
参考来源:Drugs Fut 1977,1(1),23
📄 详细内容
合成路线:The methylation of ethyl 4-nitrophenylacetate (I) with NaH - ICH3 in DMF - toluene to ethyl 2-(4-nitrophenyl)propionate (II),which was reduced with H2 over Pd/C in EtOH - H2O to ethyl 2-(4-aminophenyl)propionate (III) (HCl deriv.,m.p.137-40 C).This product was acetylated with acetic anhydride to ethyl 2-(acetylaminophenyl) propionate (IV),m.p.88-90 C,which was chlorinated with Cl2 in acetic acid to ethyl 2-(3-chloro-4-acetylaminophenyl)propionate (V),b.p.155-60 C/0.7 mm; this,in turn,was hydrolyzed with HCl in EtOH to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI),m.p.164-8 C.The last step being the reaction of the preceding intermediate with cis-1,4-dichloro (or dibromo)-2-butene (A) in DMF and Na2CO3 to ethyl 2-(3-chloro-4-(3-pyrrolinyl)phenyl)propionate (VII),b.p.128-33 C/0.25 mm; followed by hydrolysis with KOH in EtOH - H2O.The acetylation of ethyl 4-aminophenylacetate (VIII) with acetic anhydride to ethyl 4-acetylaminophenylacetate (IX),m.p.75-8 C,followed by methylation with ICH3 and Na in liquid NH3 to ethyl 2-(4-acetylaminophenyl)propionate (IV),already obtained.
参考文献标题:Tertiary amino phenyl acetic acids
文献作者:Carney,R.W.J.; de Stevens,G.
参考来源:CH 574926; CH 577968; CH 578523; CH 581103; CH 581104; US 3641040
合成路线:The reaction of 2,4-dichloronitrobenzene (X) with sodium diethyl methylmalonate (B) in DMF to diethyl 2-(4-nitro-3-chlorophenyl)-2-methyl-malonate (XI),b.p.147-8 C/0.25 mm,followed hydrolysis,decarboxylation and esterification to ethyl 2-(3-chloro-4-nitrophenyl)propionate (XII),b.p.138-42 C /0.25 mm; which,in turn,was reduced as before to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI).Conversely,the diethyl 2-(4-nitro-3-chlorophenyl)-2-methylmalonate (XI),already obtained before,could be hydrogenated first to diethyl 2-(4-amino-3-chlorophenyl)-2-methylmalonate (XIII),b.p.180-5 C/0.25 mm,and then hydrolyzed,decarboxylated and esterified again to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI).
参考文献标题:Potent nonsteroidal anti-inflammatory agent,2-[3-chloro-4-(3-pyrrolin-1-yl)phenyl]propionic acid
文献作者:Carney,R.W.; et al.
参考来源:Experientia 1973,29(8),938
产品链接: CAS No. 31793-07-4››