Pirbuterol hydrochloride, CP-24314-1, Exirel
盐酸吡啶丙胺 6-2-(tert-丁胺)-1-羟基-2-(羟甲基)吡啶-3-醇 Chemical Name: 2-tert-Butylamino-1-(5-hydroxy-6-hydroxymethyl-2-pyridyl)ethanol dihydrochloride
CAS No. 38029-10-6, 38677-81-5 (free base)
项目整合开发状态: Launched-1983
项目研究机构: Pfizer (Originator)
合成路线:A new method for the synthesis of pirbuterol hydrochloride has been described:By reaction of 2-phenyl-4H-1,3-dioxino[5,4-b]pyridine-6-carbaldehyde (I) with methyltriphenylphosphonium bromide (II) and NaOH in toluene to give 2-phenyl-6-vinyl-4H-1,3-dioxino[5,4-b]pyridine (III),which is treated with m-chloroperbenzoic acid (IV) in methylene chloride to give 6-(1,2-epoxyethyl)-2-phenyl-4H-1,3-dioxino[5,4-b]pyridine N-oxide (V).Compound (V) can also be obtained from 6-(1,2-epoxyethyl)-2-phenyl-4H-1,3-dioxino[5,4-b]pyridine (VI) by reaction with m-chloroperbenzoic acid (IV) as before.The reaction of (V) with tert-butylamine (VII) in methanol affords 6-(1-hydroxy-2-tert-butylaminoethyl)-2-phenyl-4H-1,3-dioxino[5,4-b]pyridine N-oxide (VIII),which is first treated with H2 over Pd/C in methanol and then with HCl in ethyl acetate to give pirbuterol hydrochloride.
📌 参考资料/链接：
参考文献标题:Process and intermediates for preparing pirbuteol and analogs
文献作者:Masset,S.S.; Cue,B.W.(Pfizer Inc.)
参考来源:EP 0058069; EP 0058070; EP 0058071; EP 0058072; JP 57150665
📄 详细内容
合成路线:The reaction of 3-hydroxypyridine (I) first with formaldehyde and NaOH in water,and then with benzyl bromide (A) in ethanol gives 3-benzyloxy-2,6-bis(hydroxymethyl)pyridine hydrochloride (II),which is oxidized with MnO2 in refluxing benzene yielding 2-hydroxmethyl-3-benzyloxy-6-pyridincarboxaldehyde (III).The condensation of (III) with tertbutylisonitrile (B) and acetic acid in refluxing CHCl3 affords N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-acetoxyacetamide (IV),which is hydrolyzed with 12N HCl yielding N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-hydroxyacetamide (V).The reduction of the amide group of (V) with diborane in THF gives 2-hydroxymethyl-3-benzyloxy-6-(1-hydroxy-2-tertbutylaminoethyl)pyridine (VI),which is finally debenzylated with H2 over Pd/C in methanol.
参考文献标题:Pirbuterol
文献作者:Castar,J.; Thorpe,P.
参考来源:Drugs Fut 1977,2(1),60
合成路线:The reaction of 3-hydroxypyridine (I) first with formaldehyde and NaOH in water,and then with benzyl bromide (A) in ethanol gives 3-benzyloxy-2,6-bis(hydroxymethyl)pyridine hydrochloride (II),which is oxidized with MnO2 in refluxing benzene yielding 2-hydroxmethyl-3-benzyloxy-6-pyridincarboxaldehyde (III).The condensation of (III) with tertbutylisonitrile (B) and acetic acid in refluxing CHCl3 affords N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-acetoxyacetamide (IV),which is hydrolyzed with 12N HCl yielding N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-hydroxyacetamide (V).The reduction of the amide group of (V) with diborane in THF gives 2-hydroxymethyl-3-benzyloxy-6-(1-hydroxy-2-tertbutylaminoethyl)pyridine (VI),which is finally debenzylated with H2 over Pd/C in methanol.
参考文献标题:2-Hydroxymethyl-3-hydroxy-6-(1-hydroxy-2-aminoethyl)pyridines
文献作者:Barth,W.
参考来源:DE 2204195; FR 2125309; GB 1367668; GB 1367669; US 3700681; US 3763173
产品链接: CAS No. 38029-10-6›› 产品链接: CAS No.38677-81-5››