LY-341122

合成路线:3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia.Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V).Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI),which was reduced to alcohol (VII) with borane in THF.Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII).This was coupled with 4-hydroxybenzaldehyde (IX),yielding ether (X).Finally,reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.

参考文献标题:Method for treating pain
文献作者:Shannon,H.E.; Panetta,J.A.(Eli Lilly and Company)
参考来源:WO 9909980


合成路线:3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia.Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V).Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI),which was reduced to alcohol (VII) with borane in THF.Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII).This was coupled with 4-hydroxybenzaldehyde (IX),yielding ether (X).Finally,reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.

参考文献标题:Oxazoles,thiazoles,oxazolines,oxadiazoles and benzoxazoles useful as neuro-protective agents
文献作者:Heinz,L.J.; Panetta,J.A.; Phillips,M.L.; Rieck,J.A.; Rizzo,J.R.; Shadle,J.K.; Varie,D.L.; Anderson,B.A.(Eli Lilly and Company)
参考来源:EP 0908454; WO 9918091


合成路线:3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia.Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V).Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI),which was reduced to alcohol (VII) with borane in THF.Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII).This was coupled with 4-hydroxybenzaldehyde (IX),yielding ether (X).Finally,reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.

参考文献标题:Method for treating pain
文献作者:Panetta,J.A.; Shannon,H.E.(Eli Lilly and Company)
参考来源:WO 9909829


合成路线:3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia.Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V).Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI),which was reduced to alcohol (VII) with borane in THF.Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII).This was coupled with 4-hydroxybenzaldehyde (IX),yielding ether (X).Finally,reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.
参考文献标题:Method for treating neuropathic pain
文献作者:Shannon,H.E.; Panetta,J.A.(Eli Lilly and Company)
参考来源:WO 9909979