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【结 构 式】 
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【药物名称】DZ-3514 【化学名称】N-Methyl-2-[3-[N-(N-methyl-N-phenylcarbamoylmethyl)-N-[2-[3-(3-methylphenyl)ureido]acetyl]amino]phenoxy]-N-phenylacetamide 【CA登记号】 【 分 子 式 】C34H35N5O5 【 分 子 量 】593.68855 |
【开发单位】Daiichi Pharmaceutical (Originator) 【药理作用】Antiulcer Drugs, GASTROINTESTINAL DRUGS, CCK2 (CCKB/Gastrin) Antagonists |
合成路线1
Alkylation of 3-nitrophenol (I) with methyl bromoacetate (II) in the presence of K2CO3 provided phenoxyacetate (III). Then, reduction of the nitro group of (III) by hydrogenation on Pd/C gave amine (IV), which was subsequently condensed with N-tert-butoxycarbonyl glycine (V) on treatment with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (EDC) to afford amide (VI). Alkylation with bromoacetamide (VII) in the presence of NaH in THF provided (VIII), and removal of the Boc protecting group with trifluoroacetic acid gave amine (IX). This amine was condensed with 3-tolyl isocyanate (X) to give urea (XI). Then, alkaline hydrolysis of the ester group afforded acid (XII), which was finally condensed with N-methylaniline (XIII) to yield the target compound.
| 【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 . |
| 【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 . |
| 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) | 18076 | Metanitrophenol; 3-nitrophenol | 554-84-7 | C6H5NO3 | 详情 | 详情 |
| (II) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
| (III) | 18077 | methyl 2-(3-nitrophenoxy)acetate | C9H9NO5 | 详情 | 详情 | |
| (IV) | 18078 | methyl 2-(3-aminophenoxy)acetate | C9H11NO3 | 详情 | 详情 | |
| (V) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (V) | 18068 | 2-bromo-N-methyl-N-phenylacetamide | C9H10BrNO | 详情 | 详情 | |
| (VI) | 18079 | methyl 2-[3-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)phenoxy]acetate | C16H22N2O6 | 详情 | 详情 | |
| (VIII) | 18080 | methyl 2-(3-[[2-[(tert-butoxycarbonyl)amino]acetyl][2-(methylanilino)-2-oxoethyl]amino]phenoxy)acetate | C25H31N3O7 | 详情 | 详情 | |
| (IX) | 18081 | methyl 2-(3-[(2-aminoacetyl)[2-(methylanilino)-2-oxoethyl]amino]phenoxy)acetate | C20H23N3O5 | 详情 | 详情 | |
| (X) | 18071 | m-Tolyl Isocyanate; 1-isocyanato-3-methylbenzene; 3-methylphenyl isocyanate | 621-29-4 | C8H7NO | 详情 | 详情 |
| (XI) | 18082 | methyl 2-[3-([2-(methylanilino)-2-oxoethyl][2-[(3-toluidinocarbonyl)amino]acetyl]amino)phenoxy]acetate | C28H30N4O6 | 详情 | 详情 | |
| (XII) | 18083 | 2-[3-([2-(methylanilino)-2-oxoethyl][2-[(3-toluidinocarbonyl)amino]acetyl]amino)phenoxy]acetic acid | C27H28N4O6 | 详情 | 详情 | |
| (XIII) | 10409 | N-Methyl-N-phenylamine; N-methylaniline; Monomethylaniline | 100-61-8 | C7H9N | 详情 | 详情 |