|
【结 构 式】 
|
【分子编号】41948 【品名】3-nitrobenzenesulfonyl chloride 【CA登记号】121-51-7 |
【 分 子 式 】C6H4ClNO4S 【 分 子 量 】221.6208 【元素组成】C 32.52% H 1.82% Cl 16% N 6.32% O 28.88% S 14.47% |
合成路线1
该中间体在本合成路线中的序号：(V)Deprotection of the benzyloxycarbonyl piperazine (I) by catalytic hydrogenolysis provided the secondary amine (II), which was then acylated by benzyloxyacetyl chloride (III) to afford amide (IV). After activation of the hydroxyl group of (IV) as the sulfonate (VI) by treatment with 3-nitrobenzenesulfonyl chloride (V), its displacement with ammonium hydroxide provided the amine (VII). The O-benzyl group of (VII) was then removed by hydrogenolysis, yielding alcohol (VIII). Finally, acylation of the primary amino group of (VIII) with ethyl dithioacetate (IX) in the presence of KOH and NaF gave rise to the title thioacetamide.
| 【1】 Hester, J.B. Jr.; Perricone, S.C.; Nidy, E.G.; Poel, T.-J. (Pharmacia Corp.); Oxazolidinone antibacterial agents having a thiocarbonyl functionality. EP 0984947; JP 2002501530; US 6218413; WO 9854161 . |
| 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) | 18386 | benzyl 4-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]-1-piperazinecarboxylate | C22H24FN3O5 | 详情 | 详情 | |
| (II) | 55847 | (5R)-3-[3-fluoro-4-(1-piperazinyl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C14H18FN3O3 | 详情 | 详情 | |
| (III) | 10493 | 2-(Benzyloxy)acetyl chloride; Benzyloxyacetyl chloride | 19810-31-2 | C9H9ClO2 | 详情 | 详情 |
| (IV) | 55848 | (5R)-3-(4-{4-[2-(benzyloxy)acetyl]-1-piperazinyl}-3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C23H26FN3O5 | 详情 | 详情 | |
| (V) | 41948 | 3-nitrobenzenesulfonyl chloride | 121-51-7 | C6H4ClNO4S | 详情 | 详情 |
| (VI) | 55849 | [(5R)-3-(4-{4-[2-(benzyloxy)acetyl]-1-piperazinyl}-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl 3-nitrobenzenesulfonate | C29H29FN4O9S | 详情 | 详情 | |
| (VII) | 55850 | (5S)-5-(aminomethyl)-3-(4-{4-[2-(benzyloxy)acetyl]-1-piperazinyl}-3-fluorophenyl)-1,3-oxazolidin-2-one | C23H27FN4O4 | 详情 | 详情 | |
| (VIII) | 17828 | (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-glycoloyl-1-piperazinyl)phenyl]-1,3-oxazolidin-2-one | C16H21FN4O4 | 详情 | 详情 | |
| (IX) | 55851 | Ethyl dithioacetate | C4H8S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Condensation of 3-nitrobenzenesulfonyl chloride (I) with tetrahydroquinoline (II) in the presence of pyridine gave sulfonamide (III). Reduction of the nitro group of (III) with stannous chloride produced the aniline derivative (IV). The title compound was then obtained by reductive alkylation of amine (IV) with 4-formylimidazole (V) using sodium triacetoxyborohydride as the reducing reagent.
| 【1】 Hunt, J.T.; Manne, V.; Ding, C.Z.; Ricca, C.; 3-Imidazolylmethylaminophenylsulfonyltetrahydroquinolines, a novel series of farnesyltransferase inhibitors. Bioorg Med Chem Lett 2000, 10, 3, 273. |
| 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) | 41948 | 3-nitrobenzenesulfonyl chloride | 121-51-7 | C6H4ClNO4S | 详情 | 详情 |
| (II) | 23859 | 1,2,3,4-tetrahydroquinoline | 635-46-1 | C9H11N | 详情 | 详情 |
| (III) | 41949 | 1-[(3-nitrophenyl)sulfonyl]-1,2,3,4-tetrahydroquinoline | C15H14N2O4S | 详情 | 详情 | |
| (IV) | 41950 | 3-[3,4-dihydro-1(2H)-quinolinylsulfonyl]phenylamine; 3-[3,4-dihydro-1(2H)-quinolinylsulfonyl]aniline | C15H16N2O2S | 详情 | 详情 | |
| (V) | 41951 | 1H-imidazole-5-carbaldehyde | 3034-50-2 | C4H4N2O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(X)The protection of the NH group of N-[3(S)-(dibenzylamino)-2(R)-hydroxy-4-phenylbutyl]-N-isobutylamine (I) with Boc2O and TEA in THF gives the carbamate (II), which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol to yield the primary amine (III). The condensation of (III) with N-(benzyloxycarbonyl)-L-tert-leucine (IV) by means of EDC, HOBT and NMM in DMF affords the leucinamide (V), which is deprotected with H2 and Pd/C in methanol, providing the intermediate (VI). The acylation of the free amino group of (VI) with chloroacetyl chloride (VII) and KHCO3 in ethyl acetate/water gives the chloroacetamide (VIII), which is treated with HCl in ethyl acetate/dioxane in order to eliminate the Boc protecting group and yield the secondary amine (IX). The reaction of (IX) with 3-nitrophenylsulfonyl chloride (X) and K2CO3 in THF/water gives the sulfonamide (XI), which is treated with 3-fluorobenzylamine (XII) in refluxing THF to afford the glycyl-tert-leucyl derivative (XIII). Finally, the reduction of the nitro group of (XIII) with H2 over Pd/C in methanol provides the target 3-aminophenylsulfonamide.
| 【1】 Kaltenbach, R.F.; Trainor, G.L. (DuPont Pharmaceuticals Co.); Bis-amino acid sulfonamides containing N-terminally A substd. benzyl group as HIV protease inhibitors. EP 1140983; WO 0042060 . |
| 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) | 48825 | (2R,3S)-N(3),N(3)-dibenzyl-N(1)-isobutyl-2-methyl-4-phenyl-1,3-butanediamine; N,N-dibenzyl-N-[(1S,2R)-1-benzyl-3-(isobutylamino)-2-methylpropyl]amine | C29H38N2 | 详情 | 详情 | |
| (II) | 48826 | tert-butyl (2R,3S)-3-(dibenzylamino)-2-methyl-4-phenylbutyl(isobutyl)carbamate | C34H46N2O2 | 详情 | 详情 | |
| (III) | 48827 | tert-butyl (2R,3S)-3-amino-2-methyl-4-phenylbutyl(isobutyl)carbamate | C20H34N2O2 | 详情 | 详情 | |
| (IV) | 48828 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3,3-dimethylbutyric acid | C14H19NO4 | 详情 | 详情 | |
| (V) | 48829 | benzyl (1S)-1-[([(1S,2R)-1-benzyl-3-[(tert-butoxycarbonyl)(isobutyl)amino]-2-methylpropyl]amino)carbonyl]-2,2-dimethylpropylcarbamate | C34H51N3O5 | 详情 | 详情 | |
| (VI) | 48830 | tert-butyl (2R,3S)-3-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-2-methyl-4-phenylbutyl(isobutyl)carbamate | C26H45N3O3 | 详情 | 详情 | |
| (VII) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VIII) | 48831 | tert-butyl (2R,3S)-3-([(2S)-2-[(2-chloroacetyl)amino]-3,3-dimethylbutanoyl]amino)-2-methyl-4-phenylbutyl(isobutyl)carbamate | C28H46ClN3O4 | 详情 | 详情 | |
| (IX) | 48832 | (2S)-N-[(1S,2R)-1-benzyl-3-(isobutylamino)-2-methylpropyl]-2-[(2-chloroacetyl)amino]-3,3-dimethylbutanamide | C23H38ClN3O2 | 详情 | 详情 | |
| (X) | 41948 | 3-nitrobenzenesulfonyl chloride | 121-51-7 | C6H4ClNO4S | 详情 | 详情 |
| (XI) | 48833 | (2S)-N-((1S,2R)-1-benzyl-3-[isobutyl[(3-nitrophenyl)sulfonyl]amino]-2-methylpropyl)-2-[(2-chloroacetyl)amino]-3,3-dimethylbutanamide | C29H41ClN4O6S | 详情 | 详情 | |
| (XII) | 48834 | 3-Fluorobenzylamine | 100-82-3 | C7H8FN | 详情 | 详情 |
| (XIII) | 48835 | (2S)-N-((1S,2R)-1-benzyl-3-[isobutyl[(3-nitrophenyl)sulfonyl]amino]-2-methylpropyl)-2-([2-[(3-fluorobenzyl)amino]acetyl]amino)-3,3-dimethylbutanamide | C36H48FN5O6S | 详情 | 详情 |