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The diazotation of 3-(4-aminobenzoylamino)propionic acid (I) with NaNO2 and HCl gives the corresponding diazonium salt (II), which is then condensed with salicylic acid.

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The diazotation of 4-aminohippuric acid (I) with NaNO2 and HCl gives the corresponding diazonium salt (II), which is then condensed with salicylic acid.

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It is prepared by treatment of 2-hydroxybenzoic acid (I) with phosphorous pentachloride. The reaction involves a first stage in which (I) is converted by PCl5 to the corresponding acyl chloride (II) upon release of phosphorous oxychloride, which reacts immediately with the free phenolic group of (II), giving rise to the acid trichloride (III). In a second stage, (III) is hydrolyzed with enough water to give the 2-phosphonoxybenzoic acid (IV). The reaction is carried out in a one-step process, which involves chlorination, phosphonation and hydrolysis, the isolation of the intermediate (III) being unnecessary. The final product is recovered from the reaction mixture by precipitation with a suitable inert organic solvent and is submitted to further purification.

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1) The reaction of 3-bromophthalide with 2-hydroxybenzoic acid (I), previously salified with triethylamine in refluxing acetone gives 1,3-dihydro-3-oxo-1-isobenzofuranyl 2-hydroxybenzoate (II). Compound (II) is acetylated with acetic anhydride, using sulfuric acid as catalizer.

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The antibacterial sulfonamide sulfapyridazine (I) or its sodium salt (II) is treated with sodium nitrite in the presence of hydrochloric acid to give the appropriate diazonium chloride (III). Coupling reaction with salicylic acid (IV) yields salazopyridazin.

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Diazotization of 4-[N-(4,6-dimethyl-2-pyrimidinyl)sulfamoyl]aniline (I) by means of sodium nitrite in diluted hydrochloric acid gives a corresponding diazonium salt (II), which is then reacted with salicylic acid (III) to afford the 2-hydroxy intermediate (IV). Disalazine is obtained by the reaction of (IV) with acetic anhydride or acetyl chloride.

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Horner-Emmons condensation of 4-nitrobenzophenone (IX) with triethyl phosphonoacetate produced a 2:1 mixture of Z and E nitrophenylcinnamic esters (XI) and (X). Alternatively, the desired Z isomer was obtained in a more favorable 8:1 ratio by condensation of (IX) with ethyl (trimethylsilyl)acetate under Peterson reaction conditions. Ester hydrolysis in the mixture (X) + (XI) with K2CO3 in aqueous methanol gave the corresponding mixture of carboxylic acids (XII). Optionally, the pure Z isomer could be isolated by recrystallization from EtOAc. DCC coupling of piperidine (VIII) with either the pure Z-isomer or the Z/E-mixture of carboxylic acids (XIIa-b) gave rise to the respective Z/E isomeric amides (XIIIa-b). After catalytic hydrogenation of the nitro group of (XIII), the required Z-(4-aminophenyl)cinnamamide isomer (XIV) was isolated by column chromatography. Finally, diazotization of (XIV), followed by coupling of the resultant diazonium salt (XV) to salicylic acid, furnished the title diazo compound.

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The condensation of 4-nitrobenzenesulfonamide (I) with 4-chloro-4-oxobutyric acid methyl ester (II) in refluxing pyridine gives 4-(4-nitrobenzenesulfonamido)-4-oxobutyric acid methyl ester (III), which is reduced with Fe and NH4Cl in methanol/water to yield the corresponding 4-amino derivative (IV). The diazotization of (IV) with NaNO2 and HCl affords the diazonium salt (V), which is condensed with 2-hydroxybenzoic acid (VI) to provide the azo compound (VII). Finally, this compound is hydrolyzed with NaOH to the target succinamic acid derivative.

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The diazotization of 2-(4-aminophenyl)acetic acid (I) by means of NaNO2 and HCl gives the diazonium salt (II), which is then condensed with 2-hydroxybenzoic acid (III) to provide the target azocompound.

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