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【结 构 式】 
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【分子编号】39720 【品名】2-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]acetic acid 【CA登记号】 |
【 分 子 式 】C19H21N3O5 【 分 子 量 】371.39296 【元素组成】C 61.45% H 5.7% N 11.31% O 21.54% |
合成路线1
该中间体在本合成路线中的序号：(X)Reaction of 2-nitroanisole (I) with methyl dichloroacetate (II) in the presence of potassium tert-butoxide at -5 C produced the arylacetic acid derivative (III). Hydrogenation of (III) over Pd/C produced both reduction of the nitro group and hydrogenolysis of the halogen atom to afford amine (IV), which was then condensed with o-tolyl isocyanate (V) giving urea (VI). Basic hydrolysis of the methyl ester of (VI) provided the corresponding acid (VII). This was coupled with glycine methyl ester (VIII) using EDC and HOBt to yield amide (IX). Then, ester (IX) hydrolysis with LiOH gave rise to carboxylic acid.
| 【1】 Morley, A.D.; Harris, N.V.; Astles, P.C. (Rhone-Poulenc Rorer Ltd.); Substd. beta-alanines. WO 9933789 . |
| 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) | 39714 | methyl 2-nitrophenyl ether; 1-methoxy-2-nitrobenzene | 91-23-6 | C7H7NO3 | 详情 | 详情 |
| (II) | 36413 | methyl 2,2-dichloroacetate | 116-54-1 | C3H4Cl2O2 | 详情 | 详情 |
| (III) | 39715 | methyl 2-chloro-2-(3-methoxy-4-nitrophenyl)acetate | C10H10ClNO5 | 详情 | 详情 | |
| (IV) | 39716 | methyl 2-(4-amino-3-methoxyphenyl)acetate | C10H13NO3 | 详情 | 详情 | |
| (V) | 27106 | 1-isocyanato-2-methylbenzene | 614-68-6 | C8H7NO | 详情 | 详情 |
| (VI) | 39717 | methyl 2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetate | C18H20N2O4 | 详情 | 详情 | |
| (VII) | 39718 | 2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid | C17H18N2O4 | 详情 | 详情 | |
| (VIII) | 17568 | methyl 2-aminoacetate | C3H7NO2 | 详情 | 详情 | |
| (IX) | 39719 | methyl 2-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]acetate | C20H23N3O5 | 详情 | 详情 | |
| (X) | 39720 | 2-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]acetic acid | C19H21N3O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Treatment of Wang resin with acryloyl chloride (XI) in the presence of diisopropyl ethylamine produced the acrylate bound resin (XII). Conjugate addition of 3,4-dimethoxybenzylamine (XIII) to the acrylate (XII) afforded the beta-amino ester resin (XIV). This was coupled with the intermediate carboxylic acid (X) employing O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) to furnish (XV). The title compound was finally liberated from the resin (XV) by cleavage with trifluoroacetic acid.
| 【1】 Morley, A.D.; Harris, N.V.; Astles, P.C. (Rhone-Poulenc Rorer Ltd.); Substd. beta-alanines. WO 9933789 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 39720 | 2-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]acetic acid | C19H21N3O5 | 详情 | 详情 | |
| (XI) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (XII) | 19139 | acrylic acid | 79-10-7 | C3H4O2 | 详情 | 详情 |
| (XIII) | 13920 | (3,4-Dimethoxyphenyl)methanamine; 3,4-Dimethoxybenzylamine; Veratrylamine | 5763-61-1 | C9H13NO2 | 详情 | 详情 |
| (XIV) | 39721 | N-(3,4-dimethoxybenzyl)-beta-alanine | C12H17NO4 | 详情 | 详情 | |
| (XV) | 39722 | N-(3,4-dimethoxybenzyl)-N-[2-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]acetyl]-beta-alanine | C31H36N4O8 | 详情 | 详情 |