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【结 构 式】 
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【分子编号】18363 【品名】4-chloro-2-methyl-5-(methylsulfonyl)benzoic acid 【CA登记号】 |
【 分 子 式 】C9H9ClO4S 【 分 子 量 】248.68676 【元素组成】C 43.47% H 3.65% Cl 14.26% O 25.73% S 12.89% |
合成路线1
该中间体在本合成路线中的序号：(III)The copolymerization of ethylene (III) and maleic anhydride (II) in ethylbenzene (I) by means of benzoyl peroxide (IV) at 70 C gives an ethylene/maleic anhydride copolymer (V), which is ammoniated by treating with liquid ammonia in acetone yielding the ammoniated ethylene/maleic acid copolymer (VI). Finally, this product is imidated partially by heating in refluxing xylene.
| 【1】 Asculai, S.S.; Fields, J.E.; Johnson, R.K.; Johnson, J.H.; Carboxyimidate, a low-molecular-weight polyelectrolyte with antitumor properties and low toxixity. J Med Chem 1982, 25, 9, 1060-64. |
| 【2】 Hopkins, S.J.; Castaner, J.; Serradell, M.N.; Blancafort, P.; N-137. Drugs Fut 1983, 8, 3, 210. |
| 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) | 31977 | 1-ethylbenzene | 100-41-4 | C8H10 | 详情 | 详情 |
| (II) | 11182 | 2,5-Furandione; Maleic anhydride | 108-31-6 | C4H2O3 | 详情 | 详情 |
| (III) | 18363 | 4-chloro-2-methyl-5-(methylsulfonyl)benzoic acid | C9H9ClO4S | 详情 | 详情 | |
| (IV) | 35970 | benzoyl benzenecarboperoxoate | 94-36-0 | C14H10O4 | 详情 | 详情 |
| (V) | 35971 | 3-[2-(2,5-dioxotetrahydro-3-furanyl)ethyl]-4-(1-phenylethyl)dihydro-2,5-furandione | C18H18O6 | 详情 | 详情 | |
| (VI) | 35972 | C18H26N3O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Ortho metalation of 4-chlorobenzoic acid (I) with 2 equivalents of sec-butyllithium in the presence of tetramethylethylenediamine (TMEDA) in THF at -90 C, followed by addition of methyl iodide at -80 C afforded 4-chloro-2-methylbenzoic acid (II). Chlorosulfonation of (II) with ClSO3H at 135 C provided (III), which was reduced to sulfinic acid (IV) by means of Na2SO3. Alkylation of the sodium salt of (IV) with methyl iodide in aqueous methanol yielded sulfone (V). Subsequent reaction with an excess of benzylamine at 160 C gave benzylaniline (VI), from which the benzyl group was removed by hydrogenolysis in the presence of Pd/C to afford primary amine (VII). Further esterification with a methanolic solution of HCl provided methyl ester (VIII). Conversion of amine (VIII) to pyrrolyl compound (X) was effected by treatment with 2,5-dimethoxytetrahydrofuran (IX) in the presence of 4-chloropyridine hydrochloride in refluxing dioxan. Finally, condensation with guanidine in methanol at 50 C furnished the title compound.
| 【1】 Baumgarth, M.; et al.; (2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors. J Med Chem 1997, 40, 13, 2017. |
| 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) | 18359 | p-chlorobenzoic acid; 4-chlorobenzoic acid | 74-11-3 | C7H5ClO2 | 详情 | 详情 |
| (II) | 18360 | 4-chloro-2-methylbenzoic acid | 7499-07-2 | C8H7ClO2 | 详情 | 详情 |
| (III) | 18361 | 4-chloro-5-(chlorosulfonyl)-2-methylbenzoic acid | C8H6Cl2O4S | 详情 | 详情 | |
| (IV) | 18362 | 4-chloro-2-methyl-5-sulfinobenzoic acid | C8H7ClO4S | 详情 | 详情 | |
| (V) | 18363 | 4-chloro-2-methyl-5-(methylsulfonyl)benzoic acid | C9H9ClO4S | 详情 | 详情 | |
| (VI) | 18364 | 4-(benzylamino)-2-methyl-5-(methylsulfonyl)benzoic acid | C16H17NO4S | 详情 | 详情 | |
| (VII) | 18365 | 4-amino-2-methyl-5-(methylsulfonyl)benzoic acid | C9H11NO4S | 详情 | 详情 | |
| (VIII) | 18366 | methyl 4-amino-2-methyl-5-(methylsulfonyl)benzoate | C10H13NO4S | 详情 | 详情 | |
| (IX) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (X) | 18368 | methyl 2-methyl-5-(methylsulfonyl)-4-(1H-pyrrol-1-yl)benzoate | C14H15NO4S | 详情 | 详情 |