【药物名称】Prizidilol, SKF-92657
化学结构式(Chemical Structure):
参考文献No.900353
标题:
作者:Coates, W.J.; et al.
来源:BE 830158; DE 2527066; JP 7613782; NL 7507267
合成路线图解说明:

The esterification of 3-(2-hydroxybenzoyl)propionic acid (I) with methanol - hydrogen chloride gives the corresponding methyl ester (II), which is condensed with epibromohydrin (III) by means of anhydrous K2CO3 in butanone to yield methyl 3-[2-(2,3-epoxypropoxy)benzoyl]propionate (IV). The cleavage of the epoxy ring of (IV) with tert-butylamine in refluxing methanol affords methyl 3-[2-(3-tert-butylamino-2-hydroxypropoxy)benzoyl]propionate (V), which is cyclized with hydrazine in refluxing acetic acid to give 6-[2-(3-tert-butylamino-2-hydroxypropoxy)phenyl]-4,5-dihydro-3-(2H)-pyridazinone (VI). The dehydrogenation of (VI) by means of Br2 in refluxing acetic acid, with a previous acetylation with acetic anhydride affords 6-[2-(2-acetoxy-3-N-acetyl-tert-butylaminopropoxy)phenyl]-3(2H)-pyridazinone (VII). The reaction of (VII) with P2S5 in refluxing dry pyridine yields 6-[2-(2-acetoxy-3-N-acetyl-tert-butylaminopropoxy)phenyl]-3(2H)-pyridazinethione (VIII), which is deacetylated by treatment with NaOH in refluxing water - methanol giving 6-[2-(3-tert-butylamino-2-hydroxypropoxy)phenyl-3(2H)pyridazinethione (IX). Finally this compound is treated with hydrazine hydrate at reflux temperature.

参考文献No.950100
标题:Prizidilol
作者:Blancafort, P.; Serradell, M.N.; Casta馿r, J.; Hopkins, S.J.
来源:Drugs Fut 1980,5(11),554
合成路线图解说明:

The esterification of 3-(2-hydroxybenzoyl)propionic acid (I) with methanol - hydrogen chloride gives the corresponding methyl ester (II), which is condensed with epibromohydrin (III) by means of anhydrous K2CO3 in butanone to yield methyl 3-[2-(2,3-epoxypropoxy)benzoyl]propionate (IV). The cleavage of the epoxy ring of (IV) with tert-butylamine in refluxing methanol affords methyl 3-[2-(3-tert-butylamino-2-hydroxypropoxy)benzoyl]propionate (V), which is cyclized with hydrazine in refluxing acetic acid to give 6-[2-(3-tert-butylamino-2-hydroxypropoxy)phenyl]-4,5-dihydro-3-(2H)-pyridazinone (VI). The dehydrogenation of (VI) by means of Br2 in refluxing acetic acid, with a previous acetylation with acetic anhydride affords 6-[2-(2-acetoxy-3-N-acetyl-tert-butylaminopropoxy)phenyl]-3(2H)-pyridazinone (VII). The reaction of (VII) with P2S5 in refluxing dry pyridine yields 6-[2-(2-acetoxy-3-N-acetyl-tert-butylaminopropoxy)phenyl]-3(2H)-pyridazinethione (VIII), which is deacetylated by treatment with NaOH in refluxing water - methanol giving 6-[2-(3-tert-butylamino-2-hydroxypropoxy)phenyl-3(2H)pyridazinethione (IX). Finally this compound is treated with hydrazine hydrate at reflux temperature.

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