|
【结 构 式】 
|
【分子编号】47469 【品名】3,4-dimethoxybenzenesulfonyl chloride 【CA登记号】23095-31-0 |
【 分 子 式 】C8H9ClO4S 【 分 子 量 】236.67576 【元素组成】C 40.6% H 3.83% Cl 14.98% O 27.04% S 13.55% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of allyl benzene (II) with (4-nitrophenylsulfonylimino)phenyliodinane (I) by means of Cu-OTf or Cu(OTf)2 in acetonitrile gives the sulfonyl aziridine (III), which is treated with 1-(1-naphthyl)ethylamine (IV) to yield the sulfonamide (V). The cleavage of the 4-nitrophenylsulfonyl group of (V) by means of thiophenol, DMSO and K2CO3 in hot acetonitrile affords the primary amine (VI), which is finally condensed with 3,4-dimetoxyphenylsulfonyl chloride (VII) and TEA in dichloromethane to provide the target sulfonamide.
| 【1】 Dauban, P.; et al.; N1-Arylsulfonyl-N2-(1-aryl)ethyl-3-phenylpropane-1,2-diamines as novel calcimimetics acting on the calcium sensing receptor. Bioorg Med Chem Lett 2000, 10, 17, 2001. |
| 【2】 Potier, P.J.-P.S.J.; Ruat, M.; Dauban, P.M.; Faure, H.V.; Dodd, R. (CNRS (Centre National de la Recherche Scientifique)); Aralkyl-1,2-diamines having calcimimetic activity and preparation mode. WO 0134562 . |
| 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) | 47464 | 4-nitro-N-[(E)-phenyl-lambda(3)-iodanylidene]benzenesulfonamide | C12H9IN2O4S | 详情 | 详情 | |
| (II) | 47465 | 1-allylbenzene | 300-57-2 | C9H10 | 详情 | 详情 |
| (III) | 47466 | 2-benzyl-1-[(4-nitrophenyl)sulfonyl]aziridine | C15H14N2O4S | 详情 | 详情 | |
| (IV) | 47470 | 1-(1-naphthyl)ethylamine; 1-(1-naphthyl)-1-ethanamine | C12H13N | 详情 | 详情 | |
| (V) | 47467 | N-(1-benzyl-2-[[1-(1-naphthyl)ethyl]amino]ethyl)-4-nitrobenzenesulfonamide | C27H27N3O4S | 详情 | 详情 | |
| (VI) | 47468 | N-(2-amino-3-phenylpropyl)-N-[1-(1-naphthyl)ethyl]amine; N(1)-[1-(1-naphthyl)ethyl]-3-phenyl-1,2-propanediamine | C21H24N2 | 详情 | 详情 | |
| (VII) | 47469 | 3,4-dimethoxybenzenesulfonyl chloride | 23095-31-0 | C8H9ClO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)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3
该中间体在本合成路线中的序号：(II)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 |
合成路线4
该中间体在本合成路线中的序号：(V)Coupling between N-Boc-4-piperidinol (I) and 4-fluorobenzotrifluoride (II) in the presence of cesium carbonate afforded ether (III). Subsequent acidic cleavage of the Boc protecting group of (III) furnished piperidine (IV) (1). Acylation of piperidine (IV) with 3,4-dimethoxybenzenesulfonyl chloride (V) yielded the corresponding sulfonamide (VI). Regioselective metalation of (VI) by means of tert-butyllithium, followed by quenching with dry carbon dioxide gave rise to the carboxylic acid (VII). This was converted to the corresponding acid chloride (VIII) employing oxalyl chloride, and then condensed with O-tetrahydropyranylhydroxylamine (IX). The resultant tetrahydropyranyl-protected hydroxamate (X) was finally deprotected by treatment with an in situ generated solution of methanolic HCl.
| 【1】 Barta, T.E.; et al.; Selective, orally active MMP inhibitor with an aryl backbone. Bioorg Med Chem Lett 2001, 11, 18, 2481. |
| 【2】 Villamil, C.I.; Becker, D.P.; Bedell, L.J.; Freskos, J.N.; Rao, S.N.; Getman, D.P.; Decrescenzo, G.A.; Mischke, B.V.; Barta, T.E.; McDonald, J.J. (Pharmacia Corp.); Hydroxamic acid derivs. as matrix metalloprotease inhibitors. EP 1177173; WO 0069819 . |
| 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) | 18625 | tert-butyl 4-hydroxy-1-piperidinecarboxylate | C10H19NO3 | 详情 | 详情 | |
| (II) | 52131 | 4-Fluorobenzotrifluoride; alpha,alpha-4-Tetrafluorotoluene | 402-44-8 | C7H4F4 | 详情 | 详情 |
| (III) | 52132 | tert-butyl 4-[4-(trifluoromethyl)phenoxy]-1-piperidinecarboxylate | C17H22F3NO3 | 详情 | 详情 | |
| (IV) | 52133 | 4-[4-(trifluoromethyl)phenoxy]piperidine; 4-piperidinyl 4-(trifluoromethyl)phenyl ether | C12H14F3NO | 详情 | 详情 | |
| (V) | 47469 | 3,4-dimethoxybenzenesulfonyl chloride | 23095-31-0 | C8H9ClO4S | 详情 | 详情 |
| (VI) | 52134 | 1-[(3,4-dimethoxyphenyl)sulfonyl]-4-piperidinyl 4-(trifluoromethyl)phenyl ether; 1-[(3,4-dimethoxyphenyl)sulfonyl]-4-[4-(trifluoromethyl)phenoxy]piperidine | C20H22F3NO5S | 详情 | 详情 | |
| (VII) | 52135 | 2,3-dimethoxy-6-([4-[4-(trifluoromethyl)phenoxy]-1-piperidinyl]sulfonyl)benzoic acid | C21H22F3NO7S | 详情 | 详情 | |
| (VIII) | 52136 | 2,3-dimethoxy-6-([4-[4-(trifluoromethyl)phenoxy]-1-piperidinyl]sulfonyl)benzoyl chloride | C21H21ClF3NO6S | 详情 | 详情 | |
| (IX) | 52106 | 2-(aminooxy)tetrahydro-2H-pyran; O-tetrahydro-2H-pyran-2-ylhydroxylamine | C5H11NO2 | 详情 | 详情 | |
| (X) | 52137 | 2,3-dimethoxy-N-(tetrahydro-2H-pyran-2-yloxy)-6-([4-[4-(trifluoromethyl)phenoxy]-1-piperidinyl]sulfonyl)benzamide | C26H31F3N2O8S | 详情 | 详情 |