Dabuzalgron hydrochloride, R-450, Ro-115-1240, RO-1151240
甲烷磺酰胺,N-[6-氯-3-[(4,5-二氢-1H-吡唑-2-酰基)甲氧基]-2-甲基苯基]-,盐酸盐(1:1) N-[6-氯-3-[(4,5-二氢-1H-咪唑-2-基)甲氧基]-2-甲基苯基]甲磺酰胺 Chemical Name: N-[6-Chloro-3-(4,5-dihydro-1H-imidazol-2-ylmethoxy)-2-methylphenyl]methanesulfonamide hydrochloride
CAS No. 219311-43-0, 219311-44-1 (free base)
项目整合开发状态: Phase II
项目研究机构: Chugai (Originator), Roche (Originator)
合成路线:Reaction of 2,6-dinitrotoluene (I) with hydroxylamine and KOH provides 2,4-dinitro-3-methylaniline (II).Sandmeyer reaction of aniline (II) with tert-butyl nitrite and CuCl2 leads to aryl chloride (III).Selective reduction of one nitro group by transfer hydrogenation with cyclohexene and Pd/C affords the nitro aniline (IV).Further diazotization of (IV),followed by hydrolysis of the resultant diazonium fluoroborate in aqueous H2SO4 yields 4-chloro-2-methyl-3-nitrophenol (V).The intermediate clorophenol (V) can be alternatively prepared by chlorination of 2-methyl-3-nitrophenol (VI) with N-chlorosuccinimide in the presence of triflic acid.Alkylation of phenol (V) with bromoacetonitrile produces the aryloxyacetonitrile (VII).Nitro group reduction in (VII) with Zn/AcOH,followed by acylation of the resultant aniline (VIII) with mesyl chloride in pyridine leads to sulfonamide (IX).Then,Me3Al-catalyzed addition of ethylenediamine to nitrile (IX) generates the target imidazoline,which is finally isolated as the corresponding hydrochloride salt.(1)
合成路线:In a related method,2-methyl-3-nitrophenol (I) is reduced to the corresponding amine (II) by catalytic hydrogenation over Pd/C.Alkylation of phenol (II) with bromoacetonitrile provides the aryloxyacetonitrile (III).The amino group of (III) is then acylated by methanesulfonyl chloride producing sulfonamide (IV).Subsequent chlorination of (IV) employing tert-butyl hypochlorite leads to aryl chloride (V).Nitrile (V) is further converted into imidate (VI) with HCl/EtOH.Finally,reaction of imidate (VI) with ethylenediamine provides the target imidazoline.(1)
📌 参考资料/链接：
参考文献标题:2-Imidazoline,2-oxazoline,2-thiazoline,and 4-imidazole derivs.of methylphenyl,methoxyphenyl,and aminophenyl alkylsulfonamides and ureas and their use
文献作者:Yasuda,D.M.; O'Yang,C.; Cournoyer,R.L.; Keitz,P.F.(Syntex (USA) LLC)
参考来源:EP 0887346
📄 详细内容
合成路线:Reaction of 2,6-dinitrotoluene (I) with hydroxylamine and KOH provides 2,4-dinitro-3-methylaniline (II).Sandmeyer reaction of aniline (II) with tert-butyl nitrite and CuCl2 leads to aryl chloride (III).Selective reduction of one nitro group by transfer hydrogenation with cyclohexene and Pd/C affords the nitro aniline (IV).Further diazotization of (IV),followed by hydrolysis of the resultant diazonium fluoroborate in aqueous H2SO4 yields 4-chloro-2-methyl-3-nitrophenol (V).The intermediate clorophenol (V) can be alternatively prepared by chlorination of 2-methyl-3-nitrophenol (VI) with N-chlorosuccinimide in the presence of triflic acid.Alkylation of phenol (V) with bromoacetonitrile produces the aryloxyacetonitrile (VII).Nitro group reduction in (VII) with Zn/AcOH,followed by acylation of the resultant aniline (VIII) with mesyl chloride in pyridine leads to sulfonamide (IX).Then,Me3Al-catalyzed addition of ethylenediamine to nitrile (IX) generates the target imidazoline,which is finally isolated as the corresponding hydrochloride salt.(1)
合成路线:In a related method,2-methyl-3-nitrophenol (I) is reduced to the corresponding amine (II) by catalytic hydrogenation over Pd/C.Alkylation of phenol (II) with bromoacetonitrile provides the aryloxyacetonitrile (III).The amino group of (III) is then acylated by methanesulfonyl chloride producing sulfonamide (IV).Subsequent chlorination of (IV) employing tert-butyl hypochlorite leads to aryl chloride (V).Nitrile (V) is further converted into imidate (VI) with HCl/EtOH.Finally,reaction of imidate (VI) with ethylenediamine provides the target imidazoline.(1)
参考文献标题:Dabuzalgron Hydrochloride
文献作者:Sorbera,L.A.; Castar,J.
参考来源:Drugs Fut 2004,29(3),216
产品链接: CAS No. 219311-43-0›› 产品链接: CAS No.219311-44-1››