【药物名称】Acrosoxacin, Rosoxacin, Win 35,213, Roxadyl
化学结构式(Chemical Structure):
参考文献No.900258
标题:
作者:Lesher, G.Y.; Carabateas, P.M.
来源:US 3907808
合成路线图解说明:

It can be prepared in two different ways: 1) The cyclization of 3-nitrobenzaldehyde (I), methyl propiolate (II) and ammonium acetate (III) in refluxing acetic acid gives dimethyl 1,4-dihydro-4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (IV), which is aromatized by hot nitric acid affording dimethyl 4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (V). The hydrolysis of (V) with KOH in refluxing ethanol gives the corresponding diacid (VI), which is decarboxylated by treatment with Cu2O in refluxing Dowterm A yielding 4-(3-nitrophenyl)pyridine (VII) (1). The reduction of (VII) with Fe in ethanol-water-acetic acid affords 4-(3-aminophenyl)pyridine (VIII), which is condensed with diethyl ethoxymethylenemalonate (IX) by heating a 135 C, giving diethyl 3-(4-pyridyl)anilinomethylmalonate (X). The thernal cyclization of (X) in refluxing Dowtherm A yields ethyl 1,4-dihydro-4-oxo-7-(4-pyridyl)quinoline-3-carboxylate (XI), which is finally alkylated and saponified by treatment with NaH and ethyl iodide in DMF (1-3).

参考文献No.900259
标题:
作者:
来源:CA 999002; GB 1396681; JP 7461176; US 3922278
合成路线图解说明:

It can be prepared in two different ways: 1) The cyclization of 3-nitrobenzaldehyde (I), methyl propiolate (II) and ammonium acetate (III) in refluxing acetic acid gives dimethyl 1,4-dihydro-4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (IV), which is aromatized by hot nitric acid affording dimethyl 4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (V). The hydrolysis of (V) with KOH in refluxing ethanol gives the corresponding diacid (VI), which is decarboxylated by treatment with Cu2O in refluxing Dowterm A yielding 4-(3-nitrophenyl)pyridine (VII) (1). The reduction of (VII) with Fe in ethanol-water-acetic acid affords 4-(3-aminophenyl)pyridine (VIII), which is condensed with diethyl ethoxymethylenemalonate (IX) by heating a 135 C, giving diethyl 3-(4-pyridyl)anilinomethylmalonate (X). The thernal cyclization of (X) in refluxing Dowtherm A yields ethyl 1,4-dihydro-4-oxo-7-(4-pyridyl)quinoline-3-carboxylate (XI), which is finally alkylated and saponified by treatment with NaH and ethyl iodide in DMF (1-3).

参考文献No.900260
标题:
作者:Lesher, G.Y.; Carabateas, P.M.
来源:BE 783562; CA 996117; CH 565789; CH 570398; CH 570995; DE 2224090; FR 2138003; GB 1346724; NL 206697; US 3753993
合成路线图解说明:

It can be prepared in two different ways: 1) The cyclization of 3-nitrobenzaldehyde (I), methyl propiolate (II) and ammonium acetate (III) in refluxing acetic acid gives dimethyl 1,4-dihydro-4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (IV), which is aromatized by hot nitric acid affording dimethyl 4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (V). The hydrolysis of (V) with KOH in refluxing ethanol gives the corresponding diacid (VI), which is decarboxylated by treatment with Cu2O in refluxing Dowterm A yielding 4-(3-nitrophenyl)pyridine (VII) (1). The reduction of (VII) with Fe in ethanol-water-acetic acid affords 4-(3-aminophenyl)pyridine (VIII), which is condensed with diethyl ethoxymethylenemalonate (IX) by heating a 135 C, giving diethyl 3-(4-pyridyl)anilinomethylmalonate (X). The thernal cyclization of (X) in refluxing Dowtherm A yields ethyl 1,4-dihydro-4-oxo-7-(4-pyridyl)quinoline-3-carboxylate (XI), which is finally alkylated and saponified by treatment with NaH and ethyl iodide in DMF (1-3).

参考文献No.900261
标题:
作者:
来源:JP 7611777; US 4107167
合成路线图解说明:

2) The thermal cyclization of ethyl 2-[3-(4-pyridyl)anilinomethylene]acetoacetate (XII) gives 1,4-dihydro-4-oxo-7-(4-pyridyl)-3-acetylquinoline (XIII), which is alkylated by treatment with ethyl tosylate (XIV) and K2CO3 in dMF at 100 C yielding 1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-acetylquinoline (XV). Finally the acetyl group of (XV) is oxidized to the corresponding carboxyl residue by treatment with Br2 and NaOH in water.

参考文献No.950000
标题:Rosoxacin
作者:Blancafort, P.; Serradell, M.N.; Casta馿r, J.; Neuman, M.
来源:Drugs Fut 1980,5(4),199
合成路线图解说明:

It can be prepared in two different ways: 1) The cyclization of 3-nitrobenzaldehyde (I), methyl propiolate (II) and ammonium acetate (III) in refluxing acetic acid gives dimethyl 1,4-dihydro-4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (IV), which is aromatized by hot nitric acid affording dimethyl 4-(3-nitrophenyl)pyridine-3,5-dicarbocylate (V). The hydrolysis of (V) with KOH in refluxing ethanol gives the corresponding diacid (VI), which is decarboxylated by treatment with Cu2O in refluxing Dowterm A yielding 4-(3-nitrophenyl)pyridine (VII) (1). The reduction of (VII) with Fe in ethanol-water-acetic acid affords 4-(3-aminophenyl)pyridine (VIII), which is condensed with diethyl ethoxymethylenemalonate (IX) by heating a 135 C, giving diethyl 3-(4-pyridyl)anilinomethylmalonate (X). The thernal cyclization of (X) in refluxing Dowtherm A yields ethyl 1,4-dihydro-4-oxo-7-(4-pyridyl)quinoline-3-carboxylate (XI), which is finally alkylated and saponified by treatment with NaH and ethyl iodide in DMF (1-3).

合成路线图解说明:

2) The thermal cyclization of ethyl 2-[3-(4-pyridyl)anilinomethylene]acetoacetate (XII) gives 1,4-dihydro-4-oxo-7-(4-pyridyl)-3-acetylquinoline (XIII), which is alkylated by treatment with ethyl tosylate (XIV) and K2CO3 in dMF at 100 C yielding 1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-acetylquinoline (XV). Finally the acetyl group of (XV) is oxidized to the corresponding carboxyl residue by treatment with Br2 and NaOH in water.

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