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【结 构 式】 
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【分子编号】18068 【品名】2-bromo-N-methyl-N-phenylacetamide 【CA登记号】 |
【 分 子 式 】C9H10BrNO 【 分 子 量 】228.08854 【元素组成】C 47.39% H 4.42% Br 35.03% N 6.14% O 7.01% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |
合成路线2
该中间体在本合成路线中的序号：(IV)2-Benzyloxyaniline (I) was acylated with N-tert-butoxycarbonyl glycine (II) by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.HCl (EDC) to give amide (III). Alkylation with bromoacetamide (IV) in the presence of NaH in THF provided (V), and then removal of the Boc protecting group with trifluoroacetic acid gave amine (VI). This amine was condensed with 3-tolyl isocyanate (VII) to give the phenylurea (VIII). Cleavage of the benzyl group by hydrogenolysis on Pd/C provided phenol (IX), which was alkylated with methyl bromoacetate in the presence of K2CO3 to give ether (X). Alkaline hydrolysis of the ester group gave acid (XI), which was finally condensed with N-methylaniline (XII) by means of EDC to yield the target compound.
| 【1】 Takeda, Y.; et al.; Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. Chem Pharm Bull 1998, 46, 3, 434-444. |
| 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) | 18065 | 2-(benzyloxy)aniline; 2-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (II) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (III) | 18067 | tert-butyl 2-[2-(benzyloxy)anilino]-2-oxoethylcarbamate | C20H24N2O4 | 详情 | 详情 | |
| (IV) | 18068 | 2-bromo-N-methyl-N-phenylacetamide | C9H10BrNO | 详情 | 详情 | |
| (V) | 18069 | tert-butyl 2-[2-(benzyloxy)[2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate | C29H33N3O5 | 详情 | 详情 | |
| (VI) | 18070 | 2-amino-N-[2-(benzyloxy)phenyl]-N-[2-(methylanilino)-2-oxoethyl]acetamide | C24H25N3O3 | 详情 | 详情 | |
| (VII) | 18071 | m-Tolyl Isocyanate; 1-isocyanato-3-methylbenzene; 3-methylphenyl isocyanate | 621-29-4 | C8H7NO | 详情 | 详情 |
| (VIII) | 18072 | 2-(2-(benzyloxy)[2-[(3-toluidinocarbonyl)amino]acetyl]anilino)-N-methyl-N-phenylacetamide | C32H32N4O4 | 详情 | 详情 | |
| (IX) | 18073 | 2-(2-hydroxy[2-[(3-toluidinocarbonyl)amino]acetyl]anilino)-N-methyl-N-phenylacetamide | C25H26N4O4 | 详情 | 详情 | |
| (X) | 18074 | methyl 2-[2-([2-(methylanilino)-2-oxoethyl][2-[(3-toluidinocarbonyl)amino]acetyl]amino)phenoxy]acetate | C28H30N4O6 | 详情 | 详情 | |
| (XI) | 18075 | 2-[2-([2-(methylanilino)-2-oxoethyl][2-[(3-toluidinocarbonyl)amino]acetyl]amino)phenoxy]acetic acid | C27H28N4O6 | 详情 | 详情 | |
| (XII) | 10409 | N-Methyl-N-phenylamine; N-methylaniline; Monomethylaniline | 100-61-8 | C7H9N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Coupling of 2-benzyloxyaniline (I) with N-Boc-glycine (II) by means of EDC aforded amide (III). Subsequent N-alkylation of (III) with N-methyl-N-phenyl-2-bromoacetamide (IV) in the presence of NaH provided diamide (V). Hydrogenolysis of the benzyl ether of (V) over Pd/C gave phenol derivative (VI) (1). Phenol (VI) was then alkylated with bromoamide (IV) to furnish ether (VII). After cleavage of the Boc group of (VII) with trifluoroacetic acid, the resulting amine (VIII) was reacted with carbonyldiimidazole to produce imidazolide (IX), which was subsequently coupled with aniline (X) yielding urea (XI). Finally, basic hydrolysis of the methyl ester group of (XI) gave the title carboxylic acid.
| 【1】 Yokomizo, A.; Takeda, Y.; Kawagoe, K.; et al.; Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. II. Chem Pharm Bull 1998, 46, 6, 951. |
| 【2】 Yokohama, S.; Kawagoe, K.; Takeda, Y.; Yokomizo, Y.; Yokomizo, A. (Daiichi Pharmaceutical Co., Ltd.); Aminophenol derivs.. EP 0985660; US 5919824; WO 9628416 . |
| 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) | 18065 | 2-(benzyloxy)aniline; 2-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (II) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (III) | 18067 | tert-butyl 2-[2-(benzyloxy)anilino]-2-oxoethylcarbamate | C20H24N2O4 | 详情 | 详情 | |
| (IV) | 18068 | 2-bromo-N-methyl-N-phenylacetamide | C9H10BrNO | 详情 | 详情 | |
| (V) | 18069 | tert-butyl 2-[2-(benzyloxy)[2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate | C29H33N3O5 | 详情 | 详情 | |
| (VI) | 41107 | tert-butyl 2-[2-hydroxy[2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate | C22H27N3O5 | 详情 | 详情 | |
| (VII) | 41108 | tert-butyl 2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate | C31H36N4O6 | 详情 | 详情 | |
| (VIII) | 41109 | 2-amino-N-[2-[2-(methylanilino)-2-oxoethoxy]phenyl]-N-[2-(methylanilino)-2-oxoethyl]acetamide | C26H28N4O4 | 详情 | 详情 | |
| (IX) | 41110 | N-(2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethyl)-1H-imidazole-1-carboxamide | C30H30N6O5 | 详情 | 详情 | |
| (X) | 41111 | methyl 2-(3-aminophenyl)acetate | C9H11NO2 | 详情 | 详情 | |
| (XI) | 41112 | methyl 2-[3-([[(2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethyl)amino]carbonyl]amino)phenyl]acetate | C36H37N5O7 | 详情 | 详情 |