【结 构 式】 ![]() |
【分子编号】51672 【品名】6-chloro-2-fluoro-9H-purine 【CA登记号】 |
【 分 子 式 】C5H2ClFN4 【 分 子 量 】172.5489432 【元素组成】C 34.8% H 1.17% Cl 20.55% F 11.01% N 32.47% |
合成路线1
该中间体在本合成路线中的序号:(I)The alkylation of 6-chloro-2-fluoropurine (I) with isopropanol (II) under Mitsunobu conditions gives 6-chloro-2-fluoro-9-isopropylpurine (III), which is regioselectively alkylated at the 6 position with 4-methoxybenzylamine (IV) to yield 2-fluoro-9-isopropyl-N6-(4-methoxybenzyl)adenine (V). Finally, the 2-fluoro position of (V) is aminated with perhydroazepine (VI) in n-butanol at high temperature in a sealed tube to afford the target trisubstituted purine.
【1】 Verdugo, D.E.; et al.; Discovery of estrogen sulfotransferase inhibitors from a purine library screen. J Med Chem 2001, 44, 17, 2683. |
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) | 51672 | 6-chloro-2-fluoro-9H-purine | C5H2ClFN4 | 详情 | 详情 | |
(II) | 19250 | 2-propanol | 67-63-0 | C3H8O | 详情 | 详情 |
(III) | 51673 | 6-chloro-2-fluoro-9-isopropyl-9H-purine | C8H8ClFN4 | 详情 | 详情 | |
(IV) | 15098 | 4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine | 2393-23-9 | C8H11NO | 详情 | 详情 |
(V) | 51674 | N-(2-fluoro-9-isopropyl-9H-purin-6-yl)-N-(4-methoxybenzyl)amine; 2-fluoro-9-isopropyl-N-(4-methoxybenzyl)-9H-purin-6-amine | C16H18FN5O | 详情 | 详情 | |
(VI) | 18672 | azepane | 111-49-9 | C6H13N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)2-Amino-6-chloropurine (I) is converted into the 2-fluoro analogue (II) by diazotization in the presence of fluoroboric acid. Subsequent alkylation of (II) with EtOH under Mitsunobu conditions provides the 9-ethyl purine (III).
【1】 Weigele, M.; Sawyer, T.K.; Wang, Y.; Shakespeare, W.; Bohacek, R.; Sundaramoorthi, R.; Metcalf, C.A. III (Ariad Pharmaceuticals Inc.); Novel purines. WO 0144260 . |
【2】 Weigele, M.; Sawyer, T.K.; Wang, Y.; Shakespeare, W.C.; Bohacek, R.; Sundaramoorthi, R.; Metcalf, C.A. III; Dalgarno, D.C. (Ariad Pharmaceuticals Inc.); Purine derivs.. WO 0144259 . |
【3】 Weigele, M.; Sawyer, T.K.; Wang, Y.; Shakespeare, W.C.; Bohacek, R.; Sundaramoorthi, R.; Metcalf, C.A. III; Dalgarno, D.C. (Ariad Pharmaceuticals Inc.); Purine derivs.. US 2002068721 . |