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Terbinafine hydrochloride, SF-86327, Lamisil AT, Daskil, Afogan, Lamisil

盐酸特比萘芬 特比萘芬 Chemical Name: (E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine hydrochloride; trans-N-Methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2-en-4-ynylamine hydrochloride
CAS No. 78628-80-5, 91161-71-6 (free base)
项目整合开发状态: Launched-1991
项目研究机构: Novartis (Originator), LPB (Not Determined), Galderma (Licensee), Samil (Licensee)
合成路线:The condensation of N-methyl-N-(1-naphthylmethyl)propargylamine (I) with 1-bromo-2-tert-butylacetylene (II) by means of Cu2Cl2 gives N-methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2,4-diynylamine (III),which is then reduced selectively with diisobutylaluminurn hydride in toluene.

合成路线:By reductocondensation of amino (IV) with 6,6-dimethylhept-2-en-4-ynal (VI) by means of NaBH4 in methanol.

合成路线:The condensation of propenal (VII) with tert-butylacetylene (VIII) by means of butyllithium gives 6,6-dimethylhept-1-en-4-yn-3-ol (IX),which is rearranged with HBr to the allyl isomer 6,6-dimethylhept-2-en-4-yn-1-yl bromide (X).Finally,this compound is condensed with amine (IV) by means of Na2CO3 in DMF.

合成路线:Addition of formaldehyde to benzothiophene-2-sulfonamide (I),followed by condensation with trimethyl phosphite,furnished the dimethyl (sulfonamidomethyl)phosphonate (II).The phosphonate ester function of (II) was then hydrolyzed by means of bromotrimethylsilane,producing phosphonic acid (III).This was finally coupled to 2-fluoro-4-nitrophenol (IV) using trichloroacetonitrile in hot pyridine to afford the title mono-phosphonate ester.
📌 参考资料/链接:
参考文献标题:Propenylamines,pharmaceutical compositions containing them and their use as pharmaceuticals
文献作者:Stz,A.(Novartis AG)
参考来源:EP 0024587; JP 56032440; JP 63313753; Us 4755534

📄 详细内容


合成路线:The condensation of N-methyl-N-(1-naphthylmethyl)propargylamine (I) with 1-bromo-2-tert-butylacetylene (II) by means of Cu2Cl2 gives N-methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2,4-diynylamine (III),which is then reduced selectively with diisobutylaluminurn hydride in toluene.

合成路线:The condensation of N-(1-naphthylmethyl)methylamine (IV) with formaldehyde and 5,5-dimethylhexadiine (V) by means of Cu2Cl2 also gives (III),which is then reduced selectively with diisobutylaluminum hydride in toluene.

合成路线:By reductocondensation of amino (IV) with 6,6-dimethylhept-2-en-4-ynal (VI) by means of NaBH4 in methanol.

合成路线:The condensation of propenal (VII) with tert-butylacetylene (VIII) by means of butyllithium gives 6,6-dimethylhept-1-en-4-yn-3-ol (IX),which is rearranged with HBr to the allyl isomer 6,6-dimethylhept-2-en-4-yn-1-yl bromide (X).Finally,this compound is condensed with amine (IV) by means of Na2CO3 in DMF.

参考文献标题:SF-86327
文献作者:Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1984,9(6),425


合成路线:1) The Grignard reaction of 1-bromonaphthalene (I) with Mg in THF and then with [14C]-labeled CO2 gives the corresponding 1-naphthoic acid (II),which by reaction with SO2Cl2 and then with methylamine yields [14C]-N-methyl-1-naphthalenecarboxamide (III).The reduction of (III) with LiAlH4 in refluxing THF affords the corresponding amine (IV).Finally,this compound is condensed with 1-bromo-6,6-dimethylhept-2-en-4-yne (V) by means of Na2CO3 in DMF,and treated with ethanolic HCl.

合成路线:2) By condensation of (E)-N-methyl-N-(1-naphthylmethyl)-N-(pent-2-en-4-ynyl)amine (I) with [14C]-tert-butyl-chloride (II) by means of butyllithium and diethylaluminum chloride in hexane-dichloromethane.

参考文献标题:Carbon-14 labelling of terbinafine,an antimycotic agent
文献作者:Andres,H.
参考来源:J Label Compd Radiopharm 1989,27(11),1307


合成路线:The rearrangement of 6,6-dimethylhept-1-en-4-yn-3-ol (I) (scheme 09027805a,intermediate (IX)) to 1-bromo-6,6-dimethylhept-2(E)-en-4-yne (scheme 09027805a,intermediate (X)) with HBr reports a stereoselectivity E/Z of only 3/1.An exhaustive study of this halogenation/rearrangement reaction has been performed.This reaction ((I) to chloride (II)) has been improved up to and E/Z ratio of 9/1 with reaction yields of 95%,the reaction conditions being BCl3 (1.25 molar ratio) in hexane,with a reaction temperature of 25 C.

参考文献标题:A stereoselective synthesis of (E)-1-halo-6,6-dimethyl-2-hepten-4-yne: A key intermediate for terbinafine
文献作者:Chou,S.Y.; et al.
参考来源:Tetrahedron Lett 2000,41(20),3895


合成路线:A new method for the short preparation of terbinafine has been described: Condensation of (E)-N-(3-bromoallyl)-N-methyl-N-(1-naphthyl)amine (I) with lithium tert-butylethynyl(triisopropoxy)borate (II) by means of Pd(PPh3)4,and CuI in hot DMF.

参考文献标题:Efficient coupling reactions of lithium alkynyl(triisopropoxy)borates with aryl halides: Application to the antifungal terbinafine synthesis
文献作者:Oh,C.H.; Jung,S.H.
参考来源:Tetrahedron Lett 2000,41(44),8513


合成路线:The condensation of N-methyl-N-(1-naphthylmethyl)propargylamine (I) with 1-bromo-2-tert-butylacetylene (II) by means of Cu2Cl2 gives N-methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2,4-diynylamine (III),which is then reduced selectively with diisobutylaluminurn hydride in toluene.

合成路线:The condensation of N-(1-naphthylmethyl)methylamine (IV) with formaldehyde and 5,5-dimethylhexadiine (V) by means of Cu2Cl2 also gives (III),which is then reduced selectively with diisobutylaluminum hydride in toluene.

合成路线:The condensation of propenal (VII) with tert-butylacetylene (VIII) by means of butyllithium gives 6,6-dimethylhept-1-en-4-yn-3-ol (IX),which is rearranged with HBr to the allyl isomer 6,6-dimethylhept-2-en-4-yn-1-yl bromide (X).Finally,this compound is condensed with amine (IV) by means of Na2CO3 in DMF.
参考文献标题:SF-86327 and related compounds: Synthetic methods
文献作者:Stz,A.
参考来源:Int Con Chemother 1983,1165-8


产品链接: CAS No. 78628-80-5››

产品链接: CAS No.91161-71-6››