【结 构 式】 |
【分子编号】63288 【品名】(E)-3-(4-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-2-propenoic acid 【CA登记号】 |
【 分 子 式 】C17H17NO6S 【 分 子 量 】363.39112 【元素组成】C 56.19% H 4.72% N 3.85% O 26.42% S 8.82% |
合成路线1
该中间体在本合成路线中的序号:(V)Acylation of 4-iodoaniline (I) with 3,4-dimethoxybenzenesulfonyl chloride (II), followed by basic methanolysis leads to sulfonamide (III). Heck coupling of aryl iodide (III) with acrylic acid (IV) in the presence of tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine gives the cinnamic acid derivative (V). This is then coupled to the tetrahydropyranyl-protected hydroxylamine (VI) by means of EDC/HOBt to furnish (VII). The tetrahydropyranyl hydroxamate (VII) is finally deprotected under acidic conditions to produce the title compound.
【1】 Bouchain, G.; Leit, S.; Frechette, S.; et al.; Development of potential antitumor agents. Synthesis and biological evaluation of a new set of sulfonamide derivatives as histone deacetylase inhibitors. J Med Chem 2003, 46, 5, 820. |
【2】 Lavoie, R.; Bouchain, G.; Frechette, S.; et al.; Design and synthesis of a novel class of histone deacetylase inhibitors. Bioorg Med Chem Lett 2001, 11, 21, 2847. |
【3】 Delorme, D.; Ruel, R.; Lavoie, R.; Thibault, C.; Abou-Khalil, E. (MethylGene Inc.); Inhibitors of histone deacetylase. EP 1233958; JP 2003514904; WO 0138322 . |
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) | 26393 | 4-iodoaniline; 4-iodophenylamine | 540-37-4 | C6H6IN | 详情 | 详情 |
(II) | 47469 | 3,4-dimethoxybenzenesulfonyl chloride | 23095-31-0 | C8H9ClO4S | 详情 | 详情 |
(III) | 63287 | N-(4-iodophenyl)-3,4-dimethoxybenzenesulfonamide | C14H14INO4S | 详情 | 详情 | |
(IV) | 19139 | acrylic acid | 79-10-7 | C3H4O2 | 详情 | 详情 |
(V) | 63288 | (E)-3-(4-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-2-propenoic acid | C17H17NO6S | 详情 | 详情 | |
(VI) | 52106 | 2-(aminooxy)tetrahydro-2H-pyran; O-tetrahydro-2H-pyran-2-ylhydroxylamine | C5H11NO2 | 详情 | 详情 | |
(VII) | 63289 | (E)-3-(4-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-N-(tetrahydro-2H-pyran-2-yloxy)-2-propenamide | C22H26N2O7S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(III)In a different method, p-aminocinnamic acid (I) is acylated by 3,4-dimethoxybenzenesulfonyl chloride (II) to yield sulfonamide (III). After activation of the carboxylic acid (III) with oxalyl chloride, the resultant acid chloride (IV) is condensed with hydroxylamine to furnish the target hydroxamic acid.
【1】 Harris, C.J.; Finn, P.W.; Kalvinsh, I.; Piskunova, I.; Starchenkov, I.; Watkins, C.J.; Romero-Martin, M.-R.; Moore, K.G.; Ritchie, J.; Loza, E.; Dikovska, K.; Gailite, V.; Vorona, M.; Adrianov, V.; Duffy, J.E.S. (TopoTarget A/S); Carbamic acid cpds. comprising a sulfonamide linkage as HDAC inhibitors. EP 1328510; WO 0230879 . |
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) | 63290 | (E)-3-(4-aminophenyl)-2-propenoic acid | C9H9NO2 | 详情 | 详情 | |
(II) | 47469 | 3,4-dimethoxybenzenesulfonyl chloride | 23095-31-0 | C8H9ClO4S | 详情 | 详情 |
(III) | 63288 | (E)-3-(4-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-2-propenoic acid | C17H17NO6S | 详情 | 详情 | |
(IV) | 63291 | (E)-3-(4-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-2-propenoyl chloride | C17H16ClNO5S | 详情 | 详情 |