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【结 构 式】 
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【药物名称】A-299620 【化学名称】2-Methoxy-5-[4-(3,4,5-trimethoxyphenyl)-1-methyl-1H-imidazol-5-yl]phenylamine hydrochloride 【CA登记号】324519-48-4 【 分 子 式 】C20H24ClN3O4 【 分 子 量 】405.88498 |
【开发单位】Abbott (Originator) 【药理作用】ONCOLYTIC DRUGS |
合成路线1
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
| 【1】 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.; Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem 2002, 45, 8, 1697. |
| 【2】 Wang, L.; Woods, K.W.; Li, Q.; Sham, H.L. (Abbott Laboratories Inc.); Imidazole antiproliferative agents. WO 0109103 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11136 | 3,4,5-Trimethoxybenzaldehyde | 86-81-7 | C10H12O4 | 详情 | 详情 |
| (II) | 25593 | 4-methylbenzenesulfinic acid | C7H8O2S | 详情 | 详情 | |
| (III) | 49071 | [(4-methylphenyl)sulfonyl](3,4,5-trimethoxyphenyl)methylformamide | C18H21NO6S | 详情 | 详情 | |
| (IV) | 49072 | 2-[(4-methylphenyl)sulfonyl]-2-(3,4,5-trimethoxyphenyl)acetonitrile | C18H19NO5S | 详情 | 详情 | |
| (V) | 18225 | 4-METHOXY-3-NITROBENZALDEHYDE | 31680-08-7 | C8H7NO4 | 详情 | 详情 |
| (VI) | 49073 | 2,3-dimethoxy-5-[5-(4-methoxy-3-nitrophenyl)-1-methyl-1H-imidazol-4-yl]phenyl methyl ether; 5-(4-methoxy-3-nitrophenyl)-1-methyl-4-(3,4,5-trimethoxyphenyl)-1H-imidazole | C20H21N3O6 | 详情 | 详情 |