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Sibenadet hydrochloride, AR-C68397XX(free base), FPL-68397, AR-C68397AA, Viozan

盐酸西贝奈迪 西贝奈迪 Chemical Name: 4-Hydroxy-7-[2-[2-[3-(2-phenylethoxy)propylsulfonyl]ethylamino]ethyl]benzothiazol-2(3H)-one hydrochloride
CAS No. 154189-24-9, 154189-40-9 (free base)
项目整合开发状态: Phase III
项目研究机构: AstraZeneca (Originator)
合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII),which is condensed with benzothiazolone (VIII) by means of DCC,HOBT and triethylamine in DMF yielding the correponding amide (IX).Finally,this compound is reduced with borane/THF yielding the target compound.

合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII).The condensation of sulfonylacetic acid (VII) with dimethoxybenzothiazole derivative (X) by means of DCC,HOBT and triethylamine in DMF gives the corresponding amide (XI),which is reduced with borane/THF yielding intermediate (XII).Finally,this compound is demethylated with concentrated HBr or HCl.
📌 参考资料/链接:
参考文献标题:7-(2-Aminoethyl)-benzothiazolones
文献作者:Bonnert,R.V.; Brown,R.C.; Cheshire,D.R.; Ince,F.(AstraZeneca AB)
参考来源:EP 0649418; JP 1996503923; US 5648370; WO 9324473

📄 详细内容


合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII),which is condensed with benzothiazolone (VIII) by means of DCC,HOBT and triethylamine in DMF yielding the correponding amide (IX).Finally,this compound is reduced with borane/THF yielding the target compound.

合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII).The condensation of sulfonylacetic acid (VII) with dimethoxybenzothiazole derivative (X) by means of DCC,HOBT and triethylamine in DMF gives the corresponding amide (XI),which is reduced with borane/THF yielding intermediate (XII).Finally,this compound is demethylated with concentrated HBr or HCl.

合成路线:The target compound can also be obtained by reductocondensation of benzothiazolone (VIII) with aldehyde (XIII) by means of sodium cynonoborohydride.

参考文献标题:Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases
文献作者:Bonnert,R.V.; Brown,R.C.; Cage,P.A.; et al.
参考来源:15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998,Edinburgh) 1998,Abst P.275


合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII),which is condensed with benzothiazolone (VIII) by means of DCC,HOBT and triethylamine in DMF yielding the correponding amide (IX).Finally,this compound is reduced with borane/THF yielding the target compound.

合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII).The condensation of sulfonylacetic acid (VII) with dimethoxybenzothiazole derivative (X) by means of DCC,HOBT and triethylamine in DMF gives the corresponding amide (XI),which is reduced with borane/THF yielding intermediate (XII).Finally,this compound is demethylated with concentrated HBr or HCl.

合成路线:The target compound can also be obtained by reductocondensation of benzothiazolone (VIII) with aldehyde (XIII) by means of sodium cynonoborohydride.

参考文献标题:Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases
文献作者:Bonnert,R.V.; Brown,R.C.; Chapman,D.; et al.
参考来源:15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998,Edinburgh) 1998,Abst P.276


合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII),which is condensed with benzothiazolone (VIII) by means of DCC,HOBT and triethylamine in DMF yielding the correponding amide (IX).Finally,this compound is reduced with borane/THF yielding the target compound.

合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII).The condensation of sulfonylacetic acid (VII) with dimethoxybenzothiazole derivative (X) by means of DCC,HOBT and triethylamine in DMF gives the corresponding amide (XI),which is reduced with borane/THF yielding intermediate (XII).Finally,this compound is demethylated with concentrated HBr or HCl.

参考文献标题:Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airway diseases.1.Discovery and biological evaluation of some 7-(2-aminoethyl)-4-hydroxybenzothiazol-2(3H)-one analogues
文献作者:Bonnert,R.V.; Brown,R.C.; Chapman,D.; Cheshire,D.R.; Dixon,J.; Ince,F.; Kinchin,E.C.; Lyons,A.J.; Davis,A.M.; Hallam,C.; Harper,S.T.; Unitt,J.F.; Dougall,I.G.; Jackson,D.M.; McKechnie,K.; Young,A.; Simpson,W.T.
参考来源:J Med Chem 1998,41(25),4915


合成路线:The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II),which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV).The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V),which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI).The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII),which is condensed with benzothiazolone (VIII) by means of DCC,HOBT and triethylamine in DMF yielding the correponding amide (IX).Finally,this compound is reduced with borane/THF yielding the target compound.
参考文献标题:Viozan
文献作者:Casta馿r,J.; Graul,A.
参考来源:Drugs Fut 2000,25(2),165


产品链接: CAS No. 154189-24-9››

产品链接: CAS No.154189-40-9››