合成路线:The reaction of dimethyl 2,6-dimethoxyterphthalate (I) with hydroxylamine by means of polyphosphoric acid at 70 C gives methyl 4-(N-hydroxycarbamoyl)-3,5-dimethoxybenzoate (II),which by further reaction with PPA is converted into methyl 4-amino-3,5-dimethoxybenzoate (III).The reaction of (III) with NaNO2 and HBr affords the corresponding diazonium salt,which without isolation is treated with CuBr yielding methyl-4-bromo-3,5-dimethoxybenzoate (IV).The reduction of (IV) with diisobutylaluminum hydride in THF gives 4-bromo-3,5-dimethoxybenzaldehyde (V),which is condensed with 3-methoxypropionitrile (VI) by means of sodium methoxide in refluxing methanol to yield 4-bromo-3,5-dimethoxy-alpha-(methoxymethyl)cinnamic acid nitrile (VII).Finally,this compound is cyclized with guanidine (A) by means of sodium methoxide in hot methanol DMSO.2) The hydrolysis of (IV) with KOH in ethanol gives 4-bromo-3,5-dimethoxybenzoic acid (VIII),which is treated with SOCl2 in refluxing benzene - DMF to afford 4-bromo-3,5-dimethoxybenzoylchloride (IX).Then the reduction of (IX) with H2 over Pd/BaSO4 in xylene yields (V),already obtained.
合成路线:The reaction of (V) with 3-morpholinopropionitrile (X) by means of sodium methoxide in methanol - DMSO gives 4-bromo-3,5-dimethoxy-alpha-(morpholinomethyliden)hydrocinnamic acid nitrile (XI),which by reaction with aniline (B) and HCl in refluxing isopropanol is converted into 4-bromo-3,5-dimethoxy-alpha-(anilinomethyliden)hydrocinnamic acid nitrile (XII).Finally,this compound is condensed with guanidine (A) as before.
参考文献标题:Brodimoprim
文献作者:Sweetman,A.J.; Serradell,M.N.; Castar,J.; Blancafort,P.
参考来源:Drugs Fut 1982,7(2),93
合成路线:The reaction of dimethyl 2,6-dimethoxyterphthalate (I) with hydroxylamine by means of polyphosphoric acid at 70 C gives methyl 4-(N-hydroxycarbamoyl)-3,5-dimethoxybenzoate (II),which by further reaction with PPA is converted into methyl 4-amino-3,5-dimethoxybenzoate (III).The reaction of (III) with NaNO2 and HBr affords the corresponding diazonium salt,which without isolation is treated with CuBr yielding methyl-4-bromo-3,5-dimethoxybenzoate (IV).The reduction of (IV) with diisobutylaluminum hydride in THF gives 4-bromo-3,5-dimethoxybenzaldehyde (V),which is condensed with 3-methoxypropionitrile (VI) by means of sodium methoxide in refluxing methanol to yield 4-bromo-3,5-dimethoxy-alpha-(methoxymethyl)cinnamic acid nitrile (VII).Finally,this compound is cyclized with guanidine (A) by means of sodium methoxide in hot methanol DMSO.2) The hydrolysis of (IV) with KOH in ethanol gives 4-bromo-3,5-dimethoxybenzoic acid (VIII),which is treated with SOCl2 in refluxing benzene - DMF to afford 4-bromo-3,5-dimethoxybenzoylchloride (IX).Then the reduction of (IX) with H2 over Pd/BaSO4 in xylene yields (V),already obtained.
合成路线:The reaction of (V) with 3-morpholinopropionitrile (X) by means of sodium methoxide in methanol - DMSO gives 4-bromo-3,5-dimethoxy-alpha-(morpholinomethyliden)hydrocinnamic acid nitrile (XI),which by reaction with aniline (B) and HCl in refluxing isopropanol is converted into 4-bromo-3,5-dimethoxy-alpha-(anilinomethyliden)hydrocinnamic acid nitrile (XII).Finally,this compound is condensed with guanidine (A) as before.
参考文献标题:Synthesis of 4-halo-substituted analogs of trimethropin
文献作者:Kompis,I.; Wick,A.
参考来源:Helv Chim Acta 1977,60(8),3025-34
产品链接: CAS No. 56518-41-3›› 产品链接: CAS No.56518-40-2››