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【结 构 式】 
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【分子编号】58809 【品名】allyl 3-({(tert-butoxycarbonyl)[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]amino}methyl)-5-methoxyphenylcarbamate 【CA登记号】 |
【 分 子 式 】C33H50N4O8Si 【 分 子 量 】658.86766 【元素组成】C 60.16% H 7.65% N 8.5% O 19.43% Si 4.26% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Amine (XII) was converted into allyl carbamate (XIII) by reaction with allyl chloroformate. The silylethoxymethyl protecting group of (XIII) was then removed by acidic treatment to provide alcohol (XIV), which was further activated as the corresponding mesylate (XV). Condensation of mesylate (XV) with 5-ethyl-2-mercaptothiazole (XVI) gave thioether (XVII). The N-Boc group of (XVII) was finally cleaved by treatment with trifluoroacetic acid to yield the title compound.
| 【1】 Fukami, T.; Mase, T.; Tsuchiya, Y.; Kanatani, A.; Fukuroda, T. (Banyu Pharmaceutical Co., Ltd.); Aminopyridine derivs.. EP 0889034; US 6011039; WO 9734873 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 58808 | tert-butyl 3-amino-5-methoxybenzyl[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]carbamate | C29H46N4O6Si | 详情 | 详情 | |
| (XIII) | 58809 | allyl 3-({(tert-butoxycarbonyl)[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]amino}methyl)-5-methoxyphenylcarbamate | C33H50N4O8Si | 详情 | 详情 | |
| (XIV) | 58810 | allyl 3-({(tert-butoxycarbonyl)[6-(hydroxymethyl)-4-(4-morpholinyl)-2-pyridinyl]amino}methyl)-5-methoxyphenylcarbamate | C27H36N4O7 | 详情 | 详情 | |
| (XV) | 58811 | [6-[(3-{[(allyloxy)carbonyl]amino}-5-methoxybenzyl)(tert-butoxycarbonyl)amino]-4-(4-morpholinyl)-2-pyridinyl]methyl methanesulfonate | C28H38N4O9S | 详情 | 详情 | |
| (XVI) | 58812 | 5-ethyl-1,3-thiazol-2-ylhydrosulfide; 5-ethyl-1,3-thiazole-2-thiol | C5H7NS2 | 详情 | 详情 | |
| (XVII) | 58813 | allyl 3-({(tert-butoxycarbonyl)[6-{[(5-ethyl-1,3-thiazol-2-yl)sulfanyl]methyl}-4-(4-morpholinyl)-2-pyridinyl]amino}methyl)-5-methoxyphenylcarbamate | C32H41N5O6S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Tetrahydropyran-4-carboxylic acid tert-butyl ester (I) is treated with 4-fluorophenyl disulfide (II) in the presence of LDA to produce sulfide (III), which is further oxidized to the corresponding sulfone (IV) utilizing m-chloroperbenzoic acid. Displacement of the aryl fluoride (IV) with the sodium alkoxide of 3-(dibenzylamino)-1-propanol (V) affords the amino ether (VI). Debenzylation of (VI) by hydrogenation in the presence of Pd(OH)2/C gives the primary amine (VII). This is coupled with N-Boc-D-alanine (VIII) employing EDC to provide amide (IX). Cyclization of (IX) in the presence of DMAP, NMM and Boc2O leads to the N-protected hydantoin (X). The N-Boc group of (X) is then selectively removed by HCl in dioxane to furnish (XI).
| 【1】 Becker, D.P.; Villamil, C.; Barta, T.E.; et al.; Design and synthesis of potent and selective 4,4-disubstituted alpha-sulphones hydroxamates as MMP inhibitors. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 309. |
| 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) | 58908 | tert-butyl tetrahydro-2H-pyran-4-carboxylate | C10H18O3 | 详情 | 详情 | |
| (II) | 52287 | bis(4-fluorophenyl) disulfide; 1-fluoro-4-[(4-fluorophenyl)disulfanyl]benzene | C12H8F2S2 | 详情 | 详情 | |
| (III) | 58809 | allyl 3-({(tert-butoxycarbonyl)[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]amino}methyl)-5-methoxyphenylcarbamate | C33H50N4O8Si | 详情 | 详情 | |
| (IV) | 58910 | tert-butyl 4-[(4-fluorophenyl)sulfonyl]tetrahydro-2H-pyran-4-carboxylate | C16H21FO5S | 详情 | 详情 | |
| (V) | 58911 | 3-(Dibenzylamino)-1-propanol | C17H21NO | 详情 | 详情 | |
| (VI) | 58912 | tert-butyl 4-({4-[3-(dibenzylamino)propoxy]phenyl}sulfonyl)tetrahydro-2H-pyran-4-carboxylate | C33H41NO6S | 详情 | 详情 | |
| (VII) | 58913 | tert-butyl 4-{[4-(3-aminopropoxy)phenyl]sulfonyl}tetrahydro-2H-pyran-4-carboxylate | C19H29NO6S | 详情 | 详情 | |
| (VIII) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
| (IX) | 58914 | tert-butyl 4-({4-[3-({(2R)-2-[(tert-butoxycarbonyl)amino]propanoyl}amino)propoxy]phenyl}sulfonyl)tetrahydro-2H-pyran-4-carboxylate | C27H42N2O9S | 详情 | 详情 | |
| (X) | 58915 | tert-butyl (5R)-3-[3-(4-{[4-(tert-butoxycarbonyl)tetrahydro-2H-pyran-4-yl]sulfonyl}phenoxy)propyl]-5-methyl-2,4-dioxo-1-imidazolidinecarboxylate | C28H40N2O10S | 详情 | 详情 | |
| (XI) | 58916 | tert-butyl 4-[(4-{3-[(4R)-4-methyl-2,5-dioxoimidazolidinyl]propoxy}phenyl)sulfonyl]tetrahydro-2H-pyran-4-carboxylate | C23H32N2O8S | 详情 | 详情 |