SC-56938
Chemical Name: 1-[2-(4-Benzylphenoxy)ethyl]piperidine-4-carboxylic acid ethyl ester
CAS No. 186901-93-9, 179020-29-2 (hydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:4-Hydroxydiphenylmethane (I) is condensed with tert-butyl bromoacetate (II) in the presence of NaH and Bu-4NI to form the aryloxyacetate adduct (III).Ester group reduction in (III) employing LiAlH4 provides alcohol (IV),which is further treated with p-toluenesulfonyl chloride in pyridine,yielding tosylate (V) (1,2).Finally,condensation of tosylate (V) with ethyl isonipecotate (VI) furnishes the title compound (1-3).
合成路线:Alkylation of 4-hydroxydiphenylmethane (I) with tert-butyl bromoacetate (II) in the presence of NaH and Bu4NI in DMF affords ether (III).The ester function of (III) is then reduced by LiAlH4 to furnish the primary alcohol (IV),which is subsequently activated as the corresponding tosylate (V) (1,2).Condensation of tosylate (V) with 5-azabenzimidazole (VI) gives rise to a mixture of the three possible regioisomers (VII),(VIII) and (IX),which can be separated by means of flash chromatography.The desired isomer (IX) is then converted to the N-oxide (X) employing m-chloroperbenzoic acid in CHCl3 (1-3).Finally,reaction of N-oxide (X) with cyanotrimethylsilane produces the target nitrile (3).
📌 参考资料/链接：
参考文献标题:LTA4 hydrolase inhibitor pharmaceutical compsns.and methods of use
文献作者:Chandrakumar,N.S.; Chen,B.B.; Clare,M.; Desai,B.N.; Djuric,S.W.; Docter,S.H.; Gasiecki,A.F.; Haack,R.A.; Liang,C.-D.; Miyashiro,J.M.; Penning,T.D.; Russell,M.A.; Yu,S.S.(Pfizer Inc.)
参考来源:JP 1998512542; WO 9610999
📄 详细内容
合成路线:4-Hydroxydiphenylmethane (I) is condensed with tert-butyl bromoacetate (II) in the presence of NaH and Bu-4NI to form the aryloxyacetate adduct (III).Ester group reduction in (III) employing LiAlH4 provides alcohol (IV),which is further treated with p-toluenesulfonyl chloride in pyridine,yielding tosylate (V) (1,2).Finally,condensation of tosylate (V) with ethyl isonipecotate (VI) furnishes the title compound (1-3).
合成路线:Alkylation of 4-hydroxydiphenylmethane (I) with tert-butyl bromoacetate (II) in the presence of NaH and Bu4NI in DMF affords ether (III).The ester function of (III) is then reduced by LiAlH4 to furnish the primary alcohol (IV),which is subsequently activated as the corresponding tosylate (V) (1,2).Condensation of tosylate (V) with 5-azabenzimidazole (VI) gives rise to a mixture of the three possible regioisomers (VII),(VIII) and (IX),which can be separated by means of flash chromatography.The desired isomer (IX) is then converted to the N-oxide (X) employing m-chloroperbenzoic acid in CHCl3 (1-3).Finally,reaction of N-oxide (X) with cyanotrimethylsilane produces the target nitrile (3).
参考文献标题:LTA4 hydrolase inhibitors
文献作者:Chandrakumar,N.S.; Chen,B.B.; Clare,M.; Desai,B.N.; Djuric,S.W.; Docter,S.H.; Gasiecki,A.; Haack,R.A.; Liang,C.-D.; Miyashiro,J.M.; Penning,T.D.; Russell,M.A.; Yu,S.S.(Pfizer Inc.)
参考来源:EP 0804427; EP 1221441; JP 1998512848; WO 9611192
合成路线:4-Hydroxydiphenylmethane (I) is condensed with tert-butyl bromoacetate (II) in the presence of NaH and Bu-4NI to form the aryloxyacetate adduct (III).Ester group reduction in (III) employing LiAlH4 provides alcohol (IV),which is further treated with p-toluenesulfonyl chloride in pyridine,yielding tosylate (V) (1,2).Finally,condensation of tosylate (V) with ethyl isonipecotate (VI) furnishes the title compound (1-3).
参考文献标题:Pyrrolidine and piperidine analogues of SC-57461A as potent,orally active inhibitors of leukotriene A(4) hydrolase
文献作者:Penning,T.D.; Chandrakumar,N.S.; Desai,B.N.; Djuric,S.W.; Gasiecki,A.F.; Liang,C.-D.; Miyashiro,J.M.; Russell,M.A.; Askonas,L.J.; Gierse,J.K.; Harding,E.I.; Highkin,M.K.; Kachur,J.F.; Kim,S.H.; Villani-Price,D.; Pyla,E.Y.; et al.
参考来源:Bioorg Med Chem Lett 2002,12(23),3383
产品链接: CAS No. 186901-93-9››