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Guanfacine hydrochloride, SPD-503, BS-100-141, Estulic, Tenex

盐酸胍法辛 氯酰胍 Chemical Name: N-Amidino-2,6-dichlorobenzeneacetamide monohydrochloride
CAS No. 29110-48-3, 29110-47-2 (free base)
项目整合开发状态: Launched-1979
项目研究机构: Novartis (Originator), Wyeth Consumer Healthcare (Originator), Egis (Licensee), Shire Pharmaceuticals (Formulation)
合成路线:1) By methanolysis of 2,6-dichlorophenylacetonitrile (I) by means of H2SO4 to methyl 2,6-dichlorophenylacetate (II),which is then condensed with guanidine (A) in isopropanol.2) By condensation of S-methylisothiourea (V) with 2,6-dichlorophenylacetyl chloride (VI) in acetone to afford S-methyl-N-(2,6-dichlorophenylacetyl)isothiourea (VII); this product is then treated with ammonia in isopropanol.3) By condensation of 2,6-dichlorophenylacetic acid (VIII) with guanidine (A) in toluene.
📌 参考资料/链接:
参考文献标题:Substituted phenylacethyl derivatives of guanidine,O-alkylisoureas,S-alkylisothioureas and p-benzylalkylisothioureas
文献作者:Bream,J.B.; et al.(Novartis AG)
参考来源:DE 179348; FR 1584670; GB 1235723; US 3632645

📄 详细内容


合成路线:1) By methanolysis of 2,6-dichlorophenylacetonitrile (I) by means of H2SO4 to methyl 2,6-dichlorophenylacetate (II),which is then condensed with guanidine (A) in isopropanol.2) By condensation of S-methylisothiourea (V) with 2,6-dichlorophenylacetyl chloride (VI) in acetone to afford S-methyl-N-(2,6-dichlorophenylacetyl)isothiourea (VII); this product is then treated with ammonia in isopropanol.3) By condensation of 2,6-dichlorophenylacetic acid (VIII) with guanidine (A) in toluene.

参考文献标题:Substituted phenylacetylguanidines: A new class of antihypertensive agents
文献作者:Bream,J.B.; et al.
参考来源:Arzneim-Forsch Drug Res 1975,25(10),1477


合成路线:1) By methanolysis of 2,6-dichlorophenylacetonitrile (I) by means of H2SO4 to methyl 2,6-dichlorophenylacetate (II),which is then condensed with guanidine (A) in isopropanol.2) By condensation of S-methylisothiourea (V) with 2,6-dichlorophenylacetyl chloride (VI) in acetone to afford S-methyl-N-(2,6-dichlorophenylacetyl)isothiourea (VII); this product is then treated with ammonia in isopropanol.3) By condensation of 2,6-dichlorophenylacetic acid (VIII) with guanidine (A) in toluene.

合成路线:4) By reaction of the nitrile (I) with ethyl formate (B) by means of NaOEt in ethanol to give alpha-formyl-2,6-dichlorophenylacetonitrile (III),which is condensed with guanidine hydrochloride (A) by means of NaOEt in ethanol to yield alpha-(guanidinomethylene)-2,6-dichlorophenylacetonitrile (IV); this product is finally hydrolyzed and rearranged by means of HCl.

参考文献标题:BS 100-141
文献作者:Arrigoni-Martelli,E.; Castar,J.
参考来源:Drugs Fut 1976,1(4),167


合成路线:4) By reaction of the nitrile (I) with ethyl formate (B) by means of NaOEt in ethanol to give alpha-formyl-2,6-dichlorophenylacetonitrile (III),which is condensed with guanidine hydrochloride (A) by means of NaOEt in ethanol to yield alpha-(guanidinomethylene)-2,6-dichlorophenylacetonitrile (IV); this product is finally hydrolyzed and rearranged by means of HCl.

参考文献标题:Verfahren zur Herstellung von Acylguanidinen
文献作者:Bream,J.B.; et al.
参考来源:CH 518910


合成路线:4) By reaction of the nitrile (I) with ethyl formate (B) by means of NaOEt in ethanol to give alpha-formyl-2,6-dichlorophenylacetonitrile (III),which is condensed with guanidine hydrochloride (A) by means of NaOEt in ethanol to yield alpha-(guanidinomethylene)-2,6-dichlorophenylacetonitrile (IV); this product is finally hydrolyzed and rearranged by means of HCl.
参考文献标题:Verfahren zur Herstellung von Acylguanidinen
文献作者:Bream,J.B.; et al.
参考来源:CH 511816


产品链接: CAS No. 29110-48-3››

产品链接: CAS No.29110-47-2››