【结 构 式】 |
【分子编号】18145 【品名】5-chloro-2-methyl-4-nitrobenzenediazonium 【CA登记号】 |
【 分 子 式 】C7H5ClN3O2 【 分 子 量 】198.58842 【元素组成】C 42.34% H 2.54% Cl 17.85% N 21.16% O 16.11% |
合成路线1
该中间体在本合成路线中的序号:(II)5-Chloro-4-nitro-2-methylaniline (I) was treated with NaNO2 and HCl, and to the intermediate diazonium salt (II) was treated with a mixture of NaCN and Cu2(CN)2 to afford nitrile (III). Benzylic bromination of III with N-bromosuccinimide (NBS) and a catalytic amount of benzoyl peroxide under light irradiation gave bromide (IV), which was converted into acetate (V) on reaction with sodium acetate in DMF. Basic hydrolysis of (V) with NaOH, followed by treatment with HCl, yielded isobenzofuranone (VI). Treatment with diisobutylaluminum hydride (Dibal) in toluene at -78 C effected partial reduction of lactone (VI) to the cyclic hemiacetal (VII), which was then converted into methyl acetal (VIII) by treatment with methanol and trimethyl orthoformate in the presence of p-toluenesulfonic acid. Further reaction with 2-mercapto-4-ethylthiazole (IX) and KOH in DMF provided thiazolyl thioether (X). Then, the methylacetal group was hydrolyzed with HCl in THF-acetone, and the resulting hemiacetal (XI) was oxidized with pyridinium dichromate in dichlorometane to the isobenzofuranone (XII). Reduction of the nitro group with iron powder and ammonium chloride in refluxing EtOH-H2O afforded aniline (XIII). This was condensed with mesyl chloride in the presence of triethylamine to give the bis(methanesulfonyl) compound (XIV), which was finally hydrolyzed with NaOH to the title sulfonamide.
【1】 Guay, D.; Li, C.-S.; Ouimet, N. (Merck Frosst Canada Inc.); 5-Methanesulfonamido-3H-isobenzofuran-1-ones as inhibitors of cyclooxygenase-2. US 5968958; WO 9623786 . |
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) | 18144 | 5-chloro-2-methyl-4-nitroaniline; 5-Chloro-4-nitro-o-toluidine; 5-chloro-2-methyl-4-nitrophenylamine | 13852-51-2 | C7H7ClN2O2 | 详情 | 详情 |
(II) | 18145 | 5-chloro-2-methyl-4-nitrobenzenediazonium | C7H5ClN3O2 | 详情 | 详情 | |
(III) | 18146 | 5-chloro-2-methyl-4-nitrobenzonitrile | C8H5ClN2O2 | 详情 | 详情 | |
(IV) | 18147 | 2-(bromomethyl)-5-chloro-4-nitrobenzonitrile | C8H4BrClN2O2 | 详情 | 详情 | |
(V) | 18148 | 4-chloro-2-cyano-5-nitrobenzyl acetate | C10H7ClN2O4 | 详情 | 详情 | |
(VI) | 18149 | 6-chloro-5-nitro-2-benzofuran-1(3H)-one | C8H4ClNO4 | 详情 | 详情 | |
(VII) | 18150 | 6-chloro-5-nitro-1,3-dihydro-2-benzofuran-1-ol | C8H6ClNO4 | 详情 | 详情 | |
(VIII) | 18151 | 6-chloro-1-methoxy-5-nitro-1,3-dihydro-2-benzofuran; 6-chloro-5-nitro-1,3-dihydro-2-benzofuran-1-yl methyl ether | C9H8ClNO4 | 详情 | 详情 | |
(IX) | 18152 | 4-ethyl-1,3-thiazole-2-thiol; 4-ethyl-1,3-thiazol-2-ylhydrosulfide | C5H7NS2 | 详情 | 详情 | |
(X) | 18153 | 6-[(4-ethyl-1,3-thiazol-2-yl)sulfanyl]-5-nitro-1,3-dihydro-2-benzofuran-1-yl methyl ether; 4-ethyl-2-[(3-methoxy-6-nitro-1,3-dihydro-2-benzofuran-5-yl)sulfanyl]-1,3-thiazole | C14H14N2O4S2 | 详情 | 详情 | |
(XI) | 18154 | 6-[(4-ethyl-1,3-thiazol-2-yl)sulfanyl]-5-nitro-1,3-dihydro-2-benzofuran-1-ol | C13H12N2O4S2 | 详情 | 详情 | |
(XII) | 18155 | 6-[(4-ethyl-1,3-thiazol-2-yl)sulfanyl]-5-nitro-2-benzofuran-1(3H)-one | C13H10N2O4S2 | 详情 | 详情 | |
(XIII) | 18156 | 5-amino-6-[(4-ethyl-1,3-thiazol-2-yl)sulfanyl]-2-benzofuran-1(3H)-one | C13H12N2O2S2 | 详情 | 详情 | |
(XIV) | 18157 | N-[6-[(4-ethyl-1,3-thiazol-2-yl)sulfanyl]-1-oxo-1,3-dihydro-2-benzofuran-5-yl]-N-(methylsulfonyl)methanesulfonamide | C15H16N2O6S4 | 详情 | 详情 |