Prizidilol, SKF-92657

普齐地洛Chemical Name: 1-(tert-Butylamino)-3-[2-(6-hydrazinopyridazin-3-yl)phenoxy]propan-2-ol
CAS No. 59010-44-5, 59010-45-6 (sulfate salt(2:1))
项目整合开发状态: Not Determined
项目研究机构:
合成路线: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.