A-299620-药物合成数据库

【药物名称】A-299620

化学结构式(Chemical Structure):

参考文献No.	47676
标题:	Imidazole antiproliferative agents
作者:	Wang, L.; Woods, K.W.; Li, Q.; Sham, H.L. (Abbott Laboratories Inc.)
来源:	WO 0109103

合成路线图解说明: The condensation between 3,4,5-trimethoxybenzaldehyde (I), 4-methylbenzenesulfinic acid (II) and formamide in the presence of camphorsulfonic acid gave tosyl-(3,4,5-trimethoxyphenyl)methylformamide (III), which was subsequently dehydrated to the isonitrile (IV) by treatment with POCl3 and Et3N. After conversion of 4-methoxy-3-nitrobenzaldehyde (V) to the corresponding imine with methylamine, its reaction with the tosylmethyl isonitrile (IV) gave rise to the diaryl imidazole (VI). The nitro group of (VI) was finally reduced to amine by using SnCl2 and HCl or ammonium formiate and Pd/C

参考文献No.	661648
标题:	Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation
作者:	Wang, L.; Woods, K.W.; Li, Q.; Barr, K.J.; McCroskey, R.M.; Hannick, S.M.; Gherke, L.; Credo, R.B.; Hui, Y.H.; Marsch, K.; Warner, R.; Lee, J.Y.; Zielinski-Mozng, N.; Frost, D.; Rosenberg, S.H.; Sham, H.L.
来源:	J Med Chem 2002,45(8),1697

合成路线图解说明: The condensation between 3,4,5-trimethoxybenzaldehyde (I), 4-methylbenzenesulfinic acid (II) and formamide in the presence of camphorsulfonic acid gave tosyl-(3,4,5-trimethoxyphenyl)methylformamide (III), which was subsequently dehydrated to the isonitrile (IV) by treatment with POCl3 and Et3N. After conversion of 4-methoxy-3-nitrobenzaldehyde (V) to the corresponding imine with methylamine, its reaction with the tosylmethyl isonitrile (IV) gave rise to the diaryl imidazole (VI). The nitro group of (VI) was finally reduced to amine by using SnCl2 and HCl or ammonium formiate and Pd/C

合成路线图解说明: The condensation of 3,4,5-trimethoxybenzaldehyde (I) with 4-methylphenylsulfinic acid (II) and formamide by means of hot CSA gives the adduct (III), which is treated with POCl3 in DME to yield the isonitrile (IV). The reaction of benzaldehyde (V) with methylamine and AcOH in refluxing ethanol gives the enamine (VI), which is finally cyclized with isonitrile (IV) by means of K2CO3 in ethanol/DME to afford the target 1-methylimidazole.