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Nedocromil sodium, FPL-59002KP, FPL-59002(free acid), Tilavist, Tilarin, Alocril, Abrevia(former Brand Name), Rapitil, Tilade

奈多罗米钠 奈多罗米 Chemical Name: Disodium 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate
CAS No. 69049-74-7, 69049-73-6 (free acid)
项目整合开发状态: Launched-1986
项目研究机构: Aventis Pharma (Originator), Allergan (Licensee), King Pharmaceuticals (Licensee), Elan (Comarketer)
合成路线:The alkylation of 4-(N-acetyl-N-ethylamino)-2-hydroxyacetophenone (I) with allyl bromide (II) by means of K2CO3 in DMF gives the allyl ether (III),which is isomerized by refluxing in diethylaniline to 4-(N-acetyl-N-ethylamino)-3-allyl-2-hydroxyacetophenone (IV) The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding propyl derivative (V),which is deacetylated with HBr in refluxing acetic acid water to 4-(ethylamino)-3-propyl-2-hydroxyacetophenone (VI).The addition of (VI) dimethyl acetylenedicarboxylate (VII) in refluxing ethanol affords the aminomaleate (VIII),which by cyclization witn polyphosphoric acid at 100 C gives methyl 1-ethyl-6-acetyl-7-hydroxy-4 oxo-8-propyl-4H-quinoline-2-carboxylate (IX).The condensation of (IX) with diethyl oxalate in DMF by means of NaH results in the ester of the final product (X),which is then hydrolyzed with NaHCO3 iin refluxing ethanol.
📌 参考资料/链接:
参考文献标题:Nouvelles pyranoquinol閕nones et leurs compositions pharmaceutiques
文献作者:Caims,H.; Cox,D.(Rh鬾e-Poulenc Rorer Ltd.)
参考来源:DE 2819215; ES 469391; JP 1199909; JP 53137969

📄 详细内容


合成路线:The alkylation of 4-(N-acetyl-N-ethylamino)-2-hydroxyacetophenone (I) with allyl bromide (II) by means of K2CO3 in DMF gives the allyl ether (III),which is isomerized by refluxing in diethylaniline to 4-(N-acetyl-N-ethylamino)-3-allyl-2-hydroxyacetophenone (IV) The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding propyl derivative (V),which is deacetylated with HBr in refluxing acetic acid water to 4-(ethylamino)-3-propyl-2-hydroxyacetophenone (VI).The addition of (VI) dimethyl acetylenedicarboxylate (VII) in refluxing ethanol affords the aminomaleate (VIII),which by cyclization witn polyphosphoric acid at 100 C gives methyl 1-ethyl-6-acetyl-7-hydroxy-4 oxo-8-propyl-4H-quinoline-2-carboxylate (IX).The condensation of (IX) with diethyl oxalate in DMF by means of NaH results in the ester of the final product (X),which is then hydrolyzed with NaHCO3 iin refluxing ethanol.

参考文献标题:4,6-Dioxo-4H,6H-pyrano[3,2-g]quinoline-2,8-dicarbocyclic acids
文献作者:Cairns,H.; Cox,D.(Rh鬾e-Poulenc Rorer Ltd.)
参考来源:GB 2022078


合成路线:The alkylation of 4-(N-acetyl-N-ethylamino)-2-hydroxyacetophenone (I) with allyl bromide (II) by means of K2CO3 in DMF gives the allyl ether (III),which is isomerized by refluxing in diethylaniline to 4-(N-acetyl-N-ethylamino)-3-allyl-2-hydroxyacetophenone (IV) The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding propyl derivative (V),which is deacetylated with HBr in refluxing acetic acid water to 4-(ethylamino)-3-propyl-2-hydroxyacetophenone (VI).The addition of (VI) dimethyl acetylenedicarboxylate (VII) in refluxing ethanol affords the aminomaleate (VIII),which by cyclization witn polyphosphoric acid at 100 C gives methyl 1-ethyl-6-acetyl-7-hydroxy-4 oxo-8-propyl-4H-quinoline-2-carboxylate (IX).The condensation of (IX) with diethyl oxalate in DMF by means of NaH results in the ester of the final product (X),which is then hydrolyzed with NaHCO3 iin refluxing ethanol.

参考文献标题:Nedocromil sodium
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1986,11(9),756


合成路线:The alkylation of 4-(N-acetyl-N-ethylamino)-2-hydroxyacetophenone (I) with allyl bromide (II) by means of K2CO3 in DMF gives the allyl ether (III),which is isomerized by refluxing in diethylaniline to 4-(N-acetyl-N-ethylamino)-3-allyl-2-hydroxyacetophenone (IV) The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding propyl derivative (V),which is deacetylated with HBr in refluxing acetic acid water to 4-(ethylamino)-3-propyl-2-hydroxyacetophenone (VI).The addition of (VI) dimethyl acetylenedicarboxylate (VII) in refluxing ethanol affords the aminomaleate (VIII),which by cyclization witn polyphosphoric acid at 100 C gives methyl 1-ethyl-6-acetyl-7-hydroxy-4 oxo-8-propyl-4H-quinoline-2-carboxylate (IX).The condensation of (IX) with diethyl oxalate in DMF by means of NaH results in the ester of the final product (X),which is then hydrolyzed with NaHCO3 iin refluxing ethanol.
参考文献标题:Synthesis of nedocromil sodium labelled with tritium,deuterium and carbon-14
文献作者:Wilkinson,D.J.; Lockley,W.J.S.
参考来源:J Label Compd Radiopharm 1985,22(9),883


产品链接: CAS No. 69049-74-7››

产品链接: CAS No.69049-73-6››