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【结 构 式】 
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【分子编号】68192 【品名】(2S,3R,5S)-2-((((((2S,3R,5S)-2-(acetoxymethyl)-5-(4-((Z)-((dimethylamino)methylene)amino)-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-3-yl)oxy)(2-cyanoethoxy)phosphoryl)oxy)methyl)-5-(2-(2-(4-(tert-butyl)phenoxy)acetamido)-6-oxo-1H-purin-9(6H)-yl)tetrahydrofuran-3-yl 2-(4-(tert-butyl)phenoxy)acetate 【CA登记号】 |
【 分 子 式 】C50H62N11O15P 【 分 子 量 】1088.08 【元素组成】C 55.19% H 5.74% N 14.16% O 22.06% P 2.85% |
合成路线1
该中间体在本合成路线中的序号：(IX)In one method, condensation of decitabine (I) with N,N-dimethylformamide dimethylacetal (II) gives the formamidine derivative (III), which by enzymatic acetylation with vinyl acetate in the presence of immobilized lipozyme in acetonitrile/1,4-dioxane yields the primary acetate (IV). Condensation of the deoxyribofuranose derivative (IV) with 2-cyanoethyl N,N,N’,N’-tetraisopropylphosphorodiamidate (V) in CH2Cl2 provides the phosphorodiamidate (VI), which then condenses with the deoxyguanosine derivative (VII) in CH2Cl2 to afford the trisubstituted phosphite (VIII) . oxidation of phosphite (VIII) with t-BuOOH provides the corresponding phosphate (IX), which is fully deprotected by means of NH3 in MeOH, and finally salified using naoAc in H2O/EtoH .
| 【1】 Redkar, S. Scaleup and development of a process for a low-volume subcutaneous formulation of SGI-110, a potent hypomethylating agent. 103rd Annu Meet Am Assoc Cancer Res (AACR) (March 31-April 4, Chicago) 2012, Abst. |
| 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) | 68188 | decitabine;2-Desoxy-5-azacytidine;2'-Deoxy-5-azacytidine;5-Aza-2'-deoxycytidine;5-Azadeoxycytidine;Dacogen;1,3,5-Triazin-2(1H)-one,4-amino-1-(2-deoxy-b-D-erythro-pentofuranosyl)-;b-decitabine;s-Triazin-2(1H)-one,4-amino-1-(2-deoxy-b-D-erythro-pentofuranosyl)-(7CI,8CI) | 2353-33-5 | C8H12N4O4 | 详情 | 详情 |
| (II) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (III) | 68189 | (Z)-N'-(5-((2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4-oxo-4,5-dihydro-1,3,5-triazin-2-yl)-N,N-dimethylformimidamide | C11H17N5O4 | 详情 | 详情 | |
| (IV) | 68190 | ((2S,3R,5S)-5-(4-((Z)-((dimethylamino)methylene)amino)-2-oxo-1,3,5-triazin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl acetate | C13H19N5O5 | 详情 | 详情 | |
| (V) | 48656 | 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphoramidite; 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite; Bis(diisopropylamino)-2-cyanoethoxyphosphine | 102691-36-1 | C15H32N3OP | 详情 | 详情 |
| (VI) | 68191 | ((2S,3R,5S)-3-(((2-cyanoethoxy)(diisopropylamino)phosphino)oxy)-5-(4-((Z)-((dimethylamino)methylene)amino)-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-2-yl)methyl acetate | C22H36N7O6P | 详情 | 详情 | |
| (VII) | 68194 | (2S,3R,5S)-5-(2-(2-(4-(tert-butyl)phenoxy)acetamido)-6-oxo-1H-purin-9(6H)-yl)-2-(hydroxymethyl)tetrahydrofuran-3-yl 2-(4-(tert-butyl)phenoxy)acetate | C34H41N5O8 | 详情 | 详情 | |
| (VIII) | 68193 | (2S,3R,5S)-2-((((((2S,3R,5S)-2-(acetoxymethyl)-5-(4-((Z)-((dimethylamino)methylene)amino)-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-3-yl)oxy)(2-cyanoethoxy)phosphino)oxy)methyl)-5-(2-(2-(4-(tert-butyl)phenoxy)acetamido)-6-oxo-1H-purin-9(6H)-yl)tetrahydrofuran-3-yl 2-(4-(tert-butyl)phenoxy)acetate | C50H62N11O14P | 详情 | 详情 | |
| (IX) | 68192 | (2S,3R,5S)-2-((((((2S,3R,5S)-2-(acetoxymethyl)-5-(4-((Z)-((dimethylamino)methylene)amino)-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-3-yl)oxy)(2-cyanoethoxy)phosphoryl)oxy)methyl)-5-(2-(2-(4-(tert-butyl)phenoxy)acetamido)-6-oxo-1H-purin-9(6H)-yl)tetrahydrofuran-3-yl 2-(4-(tert-butyl)phenoxy)acetate | C50H62N11O15P | 详情 | 详情 |