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【结 构 式】 
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【分子编号】11711 【品名】9H-Purine-6-thiol; 9H-Purin-6-ylhydrosulfide; 6-Mercaptopurine 【CA登记号】50-44-2 |
【 分 子 式 】C5H4N4S 【 分 子 量 】152.17972 【元素组成】C 39.46% H 2.65% N 36.82% S 21.07% |
合成路线1
该中间体在本合成路线中的序号：(I)The compound can be prepared by reacting mercaptopurine (I) with 2-chloroethylisocyanate (II) in an inert medium at a temperature from 0-50 C, preferably in the presence of an alkaline agent. Suitable inert media for the reaction are dimethylformamide, dimethylsulfoxide, phosphoric acid, hexamethyltriamide or tetramethylurea. Alkaline agents, preferably tertiary organic amines, accelerate the reaction and make the yield of the desired product higher.
| 【1】 Cerny, A.; Krepelka, J.I.; Melka, M.; Molko, M.; Pokorná, S.; Reichová, R.; Kejhová, I.; Beitová, M.; Grimová, J. (SPOFA - United Pharmaceutical Works); 6-Purinyl N-(2-chloroethyl)carbamate and thiocarbamate, a process for their preparation and use thereof. CS 249576. EP 0186454; JP 1986186382; US 4720497 . |
| 【2】 Melka, M.; Krepelka, J.; Miko, M.; CLOTURIN. Drugs Fut 1990, 15, 4, 337. |
合成路线2
该中间体在本合成路线中的序号：(IV)Treatment of N-Boc-beta-alanine (I) with bromochloromethane gives the chloromethyl ester (II), which is further converted to the iodomethyl analogue (III) under the Finkelstein halide exchange reaction conditions. Condensation of iodomethyl ester (III) with 6-mercaptopurine (IV) provides adduct (V). The N-Boc group of (V) is then removed employing trifluoroacetic acid to furnish the amine compound (VI). Finally, EDC-mediated coupling of amine (VI) with the polyethyleneglycol-bound aspartic acid (VII) affords the title mercaptopurine prodrug.
| 【1】 Choe, Y.H.; et al.; PEG prodrugs of 6-mercaptopurine (6-MP) - I: Synthesis and in vitro studies. Proc Am Assoc Cancer Res 2002, 43. |
| 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) | 26616 | N-(tert-butoxycarbonyl)-beta-alanine | 3303-84-2 | C8H15NO4 | 详情 | 详情 |
| (II) | 57758 | chloromethyl 3-[(tert-butoxycarbonyl)amino]propanoate | C9H16ClNO4 | 详情 | 详情 | |
| (III) | 57759 | iodomethyl 3-[(tert-butoxycarbonyl)amino]propanoate | C9H16INO4 | 详情 | 详情 | |
| (IV) | 11711 | 9H-Purine-6-thiol; 9H-Purin-6-ylhydrosulfide; 6-Mercaptopurine | 50-44-2 | C5H4N4S | 详情 | 详情 |
| (V) | 57760 | (9H-purin-6-ylsulfanyl)methyl 3-[(tert-butoxycarbonyl)amino]propanoate | C14H19N5O4S | 详情 | 详情 | |
| (VI) | 57761 | (9H-purin-6-ylsulfanyl)methyl 3-aminopropanoate | C9H11N5O2S | 详情 | 详情 | |
| (VII) | 65174 | C9H14NO7 | 详情 | 详情 |