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【结 构 式】 
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【分子编号】36528 【品名】methyl 4-[(2-bromo-2-methylpropanoyl)oxy]-3-(isopropylamino)benzoate 【CA登记号】 |
【 分 子 式 】C15H20BrNO4 【 分 子 量 】358.23214 【元素组成】C 50.29% H 5.63% Br 22.31% N 3.91% O 17.86% |
合成路线1
该中间体在本合成路线中的序号：(IV)The alkylation of 3-amino-4-hydroxybenzoic acid methyl ester (I) with isopropyl iodide and NaHCO3 gives 4-hydroxy-3-(isopropylamino)benzoic acid methyl ester (II), which is esterified with 2-bromoisobutyryl bromide (III) and TEA to yield 4-(2-bromoisobutyryloxy)-3-(isopropylamino)benzoic acid methyl ester (IV). The O-N migration of the 2-bromoisobutyryl group of (IV) catalyzed by acetic acid affords the 2-bromoisobutyrylamide (V), which is cyclized by means of K2CO3 to provide 4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid methyl ester (VI). Finally, this compound is condensed with guanidine and treated with MeSO3H to give the target mesylate.
| 【1】 Yamamoto, T.; et al.; An acid-catalyzed O,N-acyl migration and application to the synthesis of N-(4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl)guanidine methanesulfonate (KB-R9032), a novel Na/H exchange inhibitor. Chem Pharm Bull 1999, 47, 1, 22. |
| 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) | 19366 | methyl 3-amino-4-hydroxybenzoate | 536-25-4 | C8H9NO3 | 详情 | 详情 |
| (II) | 36527 | methyl 4-hydroxy-3-(isopropylamino)benzoate | C11H15NO3 | 详情 | 详情 | |
| (III) | 19367 | 2-bromo-2-methylpropanoyl bromide | 20769-85-1 | C4H6Br2O | 详情 | 详情 |
| (IV) | 36528 | methyl 4-[(2-bromo-2-methylpropanoyl)oxy]-3-(isopropylamino)benzoate | C15H20BrNO4 | 详情 | 详情 | |
| (V) | 36529 | methyl 3-[(2-bromo-2-methylpropanoyl)(isopropyl)amino]-4-hydroxybenzoate | C15H20BrNO4 | 详情 | 详情 | |
| (VI) | 19370 | methyl 4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate | C15H19NO4 | 详情 | 详情 | |
| (VII) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |