合成路线:Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid,but was apparently not itself evaluated for antiinflammatory activity during that study.The synthetic approach (scheme 16191901a),begins with 1-chloro-4-nitrobenzene (I),which is readily available commercially.Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base,in N,N-dimethylformamide) provides the intermediate diethyl ester (II),which is saponified in situ and then acidified to the acid (IIIa).Crude (IIIa) is then esterified to the methyl ester (IIIb),purified by column chromatography,the sequence being analogous to that of Hino et al.The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV).Finally,an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate,activated copper powder and N,N-methylformamide provides camprofen.This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).
参考文献标题:Heterocyclic compounds containing 4-aminophenyl-alkanoic acid residues with potential antiinflammatory activity.III.Derivatives of 3-hydroxyindazole
文献作者:Picciola,G.
参考来源:Boll Chim Farm 1981,120(8),458
合成路线:Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid,but was apparently not itself evaluated for antiinflammatory activity during that study.The synthetic approach (scheme 16191901a),begins with 1-chloro-4-nitrobenzene (I),which is readily available commercially.Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base,in N,N-dimethylformamide) provides the intermediate diethyl ester (II),which is saponified in situ and then acidified to the acid (IIIa).Crude (IIIa) is then esterified to the methyl ester (IIIb),purified by column chromatography,the sequence being analogous to that of Hino et al.The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV).Finally,an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate,activated copper powder and N,N-methylformamide provides camprofen.This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).
参考文献标题:Synthesis of the p-nitrophenyl ester of acridine-2-acetic acid
文献作者:Kauffman,J.M.; Taraporewala,I.B.
参考来源:J Heterocycl Chem 1982,191557
合成路线:Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid,but was apparently not itself evaluated for antiinflammatory activity during that study.The synthetic approach (scheme 16191901a),begins with 1-chloro-4-nitrobenzene (I),which is readily available commercially.Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base,in N,N-dimethylformamide) provides the intermediate diethyl ester (II),which is saponified in situ and then acidified to the acid (IIIa).Crude (IIIa) is then esterified to the methyl ester (IIIb),purified by column chromatography,the sequence being analogous to that of Hino et al.The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV).Finally,an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate,activated copper powder and N,N-methylformamide provides camprofen.This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).
参考文献标题:Non-steroidal anti-inflammatory agents.2.[(heteroarylamino)phenyl]alkanoic acids
文献作者:Hino,K.; Nakamura,H.; Nagai,Y.; Uno,H.; Nishimura,H.
参考来源:J Med Chem 1983,26222
合成路线:Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid,but was apparently not itself evaluated for antiinflammatory activity during that study.The synthetic approach (scheme 16191901a),begins with 1-chloro-4-nitrobenzene (I),which is readily available commercially.Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base,in N,N-dimethylformamide) provides the intermediate diethyl ester (II),which is saponified in situ and then acidified to the acid (IIIa).Crude (IIIa) is then esterified to the methyl ester (IIIb),purified by column chromatography,the sequence being analogous to that of Hino et al.The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV).Finally,an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate,activated copper powder and N,N-methylformamide provides camprofen.This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).
参考文献标题:CAMPROFEN
文献作者:Taraporewala,I.B.; Kauffman,J.M.
参考来源:Drugs Fut 1990,15(6),563
合成路线:Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid,but was apparently not itself evaluated for antiinflammatory activity during that study.The synthetic approach (scheme 16191901a),begins with 1-chloro-4-nitrobenzene (I),which is readily available commercially.Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base,in N,N-dimethylformamide) provides the intermediate diethyl ester (II),which is saponified in situ and then acidified to the acid (IIIa).Crude (IIIa) is then esterified to the methyl ester (IIIb),purified by column chromatography,the sequence being analogous to that of Hino et al.The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV).Finally,an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate,activated copper powder and N,N-methylformamide provides camprofen.This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).
参考文献标题:Conformational requirements at the prostaglandin cyclooxygenase receptor site: A template for designing non-steroidal anti-inflammatory drugs
文献作者:Appleton,R.A.; Brown,K.
参考来源:Prostaglandins 1979,1829
产品链接: CAS No. 15250-13-2››