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【结 构 式】 
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【分子编号】38737 【品名】ethyl 4-amino-3-methylbenzoate 【CA登记号】40800-65-5 |
【 分 子 式 】C10H13NO2 【 分 子 量 】179.21876 【元素组成】C 67.02% H 7.31% N 7.82% O 17.85% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of 4-amino-3-methylbenzoic acid ethyl ester (I) by reaction with NaNO2 and HCl catalyzed by NH4BF4 gives indazole-5-carboxylic acid ethyl ester (II), which is condensed with 2-(2-bromoethyl)-1,3-dioxolane (III) by means of sodium hexamethyldisylazane (NaHMDS) yielding the addition product (IV). The hydrolysis of the dioxolane ring of (IV) with AcOH affords the aldehyde (V), which is reductocondensed with 1-tritylimidazole-2-amine (VI) by means of NaBH(OAc)3 providing the intermediate (VII). The hydrolysis of (VII) with NaOH in ethanol/water gives the carboxylic acid (VIII), which is condensed with the 3-aminopropionic ester (IX) by means of DCC and HOBT yielding the amide (X). Finally, the tert-butyl ester of (X) is hydrolyzed with TFA in dichloromethane.
| 【1】 Petraitis, J.J.; Batt, D.G.; Houghton, G.C.; et al.; Disubstituted indazolines as potent antagonists of the integrin alphavbeta3. J Med Chem 2000, 43, 1, 41. |
| 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) | 38737 | ethyl 4-amino-3-methylbenzoate | 40800-65-5 | C10H13NO2 | 详情 | 详情 |
| (II) | 38738 | ethyl 1H-indazole-5-carboxylate | C10H10N2O2 | 详情 | 详情 | |
| (III) | 15724 | 2-(2-bromoethyl)-1,3-dioxolane | 18742-02-4 | C5H9BrO2 | 详情 | 详情 |
| (IV) | 38739 | ethyl 1-[2-(1,3-dioxolan-2-yl)ethyl]-1H-indazole-5-carboxylate | C15H18N2O4 | 详情 | 详情 | |
| (V) | 38740 | ethyl 1-(3-oxopropyl)-1H-indazole-5-carboxylate | C13H14N2O3 | 详情 | 详情 | |
| (VI) | 38741 | 1-trityl-1H-imidazol-2-amine; 1-trityl-1H-imidazol-2-ylamine | C22H19N3 | 详情 | 详情 | |
| (VII) | 38742 | ethyl 1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazole-5-carboxylate | C35H33N5O2 | 详情 | 详情 | |
| (VIII) | 38743 | 1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazole-5-carboxylic acid | C14H15N5O2 | 详情 | 详情 | |
| (IX) | 36588 | tert-butyl (2S)-3-amino-2-[(mesitylsulfonyl)amino]propanoate | C16H26N2O4S | 详情 | 详情 | |
| (X) | 38744 | tert-butyl (2S)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]-2-[(mesitylsulfonyl)amino]propanoate | C30H39N7O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)
| 【1】 Abel S, Acemoglu M, Erb B, et al. 2008. Process for the synthesis of organic compounds. US 20080200692A1. |
| 【2】 Wang YL. Li J, Kansal VK, et al. 2010. Nilotinib intermediates and preparation thereof. US 20100016590A1. |
| 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） | 67346 | (Z)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one | C10H12N2O | 详情 | 详情 | |
| (I) | 67340 | 3-fluoro-5-(trifluoromethyl)benzonitrile | 149793-69-1 | C8H3F4N | 详情 | 详情 |
| (II) | 34070 | 5-methyl-1H-imidazole | 822-36-6 | C4H6N2 | 详情 | 详情 |
| (III) | 67341 | 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzonitrile | C12H8F3N3 | 详情 | 详情 | |
| (IV) | 67342 | 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acid | C12H9F3N2O2 | 详情 | 详情 | |
| (V) | 67343 | tert-butyl (3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)carbamate | C16H18F3N3O2 | 详情 | 详情 | |
| (VI) | 67344 | 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline | 641571-11-1 | C11H10F3N3 | 详情 | 详情 |
| (VII) | 38737 | ethyl 4-amino-3-methylbenzoate | 40800-65-5 | C10H13NO2 | 详情 | 详情 |
| (VIII) | 67345 | ethyl 3-guanidino-4-methylbenzoate | C11H15N3O2 | 详情 | 详情 | |
| (IX) | 12027 | 1-(3-Pyridinyl)-1-ethanone; 1-(3-Pyridinyl)ethanone | 350-03-8 | C7H7NO | 详情 | 详情 |
| (XI) | 67347 | ethyl 4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzoate | 641569-97-3 | C19H18N4O2 | 详情 | 详情 |
| (XII) | 67348 | 4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzoic acid | 641569-94-0 | C17H14N4O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)
| 【1】 Wang YL. Li J, Kansal VK, et al. 2010. Nilotinib intermediates and preparation thereof. WO 2010009402A9. |
| 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) | 38737 | ethyl 4-amino-3-methylbenzoate | 40800-65-5 | C10H13NO2 | 详情 | 详情 |
| (II) | 67345 | ethyl 3-guanidino-4-methylbenzoate | C11H15N3O2 | 详情 | 详情 | |
| (III) | 12027 | 1-(3-Pyridinyl)-1-ethanone; 1-(3-Pyridinyl)ethanone | 350-03-8 | C7H7NO | 详情 | 详情 |
| (IV) | 67346 | (Z)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one | C10H12N2O | 详情 | 详情 | |
| (V) | 67347 | ethyl 4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzoate | 641569-97-3 | C19H18N4O2 | 详情 | 详情 |
| (VI) | 67348 | 4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzoic acid | 641569-94-0 | C17H14N4O2 | 详情 | 详情 |
| (VII) | 51493 | 3-Amino-5-bromobenzotrifluoride | 54962-75-3 | C7H5BrF3N | 详情 | 详情 |
| (VIII) | 67349 | N-(3-bromo-5-(trifluoromethyl)phenyl)-4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide | C24H17BrF3N5O | 详情 | 详情 | |
| (IX) | 34070 | 5-methyl-1H-imidazole | 822-36-6 | C4H6N2 | 详情 | 详情 |