新产品编号:2470011

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: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:Synthesis of imidazopyridines and purines as potent inhibitors of leukotriene A4 hydrolase
文献作者:Penning,T.D.; Chandrakumar,N.S.; Desai,B.N.; Djuric,S.W.; Gasiecki,A.F.; Malecha,J.W.; 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 2003,13(6),1137