Minodronic acid, Ono-5920, YH-529, YM-529, Onobis

合成路线:The cyclization of 2-aminopyridine (I) with ethyl 4-bromoacetoacetate (II) by means of NaHCO3 in hot dioxane gives the imidazopyridine (III),which is hydrolyzed at the ester function with KOH in ethanol yielding the free acid (IV) .Finally,the treatment of acid (IV) with phosphorous acid and PCl3 in chlorobenzene at 115 C,followed by hydrolysis in boiling 6N HCl yielded the target bisphosphonate.

参考文献标题:Novel preparation method of heterocyclic bis(phosphonic acid) derivs.
文献作者:Ishii,M.; Takaoka,K.(Yamanouchi Pharmaceutical Co.,Ltd.)
参考来源:JP 1999269184


合成路线:The cyclization of 2-aminopyridine (I) with ethyl 4-bromoacetoacetate (II) by means of NaHCO3 in hot dioxane gives the imidazopyridine (III),which is hydrolyzed at the ester function with KOH in ethanol yielding the free acid (IV) .Finally,the treatment of acid (IV) with phosphorous acid and PCl3 in chlorobenzene at 115 C,followed by hydrolysis in boiling 6N HCl yielded the target bisphosphonate.

参考文献标题:Studies on novel bone resorption inhibitors.II.Synthesis and pharmacological activities of fused aza-heteroarylbisphosphonate derivatives
文献作者:Takeuchi,M.; Sakamoto,S.; Kawamuki,K.; Kurihara,H.; Nakahara,H.; Isomura,Y.
参考来源:Chem Pharm Bull 1998,46(11),1703


合成路线:The cyclization of 2-aminopyridine (I) with ethyl 4-bromoacetoacetate (II) by means of NaHCO3 in hot dioxane gives the imidazopyridine (III),which is hydrolyzed at the ester function with KOH in ethanol yielding the free acid (IV) .Finally,the treatment of acid (IV) with phosphorous acid and PCl3 in chlorobenzene at 115 C,followed by hydrolysis in boiling 6N HCl yielded the target bisphosphonate.

参考文献标题:Synthesis and pharmacological activity of imidazo-[1,2-a]pyridine-2-acetic and -2,3-dicarboxylic acid and related compounds
文献作者:Casagrande,C.; et al.
参考来源:Farmaco 1968,23(12),1141


合成路线:This compound can be obtained by two related ways:1) By cyclization of aminomalonamide (I) with ethyl orthoformate (II) at 150 C catalyzed with acetic acid.2) By cyclization of (I) with ethyl formimidate (III) at 150 C catalyzed with acetic acid.

合成路线:The cyclization of 2-aminopyridine (I) with ethyl 4-bromoacetoacetate (II) by means of NaHCO3 in hot dioxane gives the imidazopyridine (III),which is hydrolyzed at the ester function with KOH in ethanol yielding the free acid (IV) .Finally,the treatment of acid (IV) with phosphorous acid and PCl3 in chlorobenzene at 115 C,followed by hydrolysis in boiling 6N HCl yielded the target bisphosphonate.
参考文献标题:
文献作者:Atsumi,T.; et al.
参考来源:JP 7688965