【结 构 式】 |
【分子编号】47055 【品名】2-[2-[2-chloro-6-(methylamino)-9H-purin-9-yl]ethyl]-1,3-propanediol 【CA登记号】 |
【 分 子 式 】C11H16ClN5O2 【 分 子 量 】285.73324 【元素组成】C 46.24% H 5.64% Cl 12.41% N 24.51% O 11.2% |
合成路线1
该中间体在本合成路线中的序号:(VII)The sodium salt of triethyl methanetricarboxylate (I) was alkylated with 1,2-dibromoethane (II) to afford bromide (III). Subsequent condensation of 6-(methylamino)-2-chloropurine (IV) with bromide (III) in the presence of K2CO3 gave adduct (V). Mono-decarbethoxylation of tricarboxylate (V) upon treatment with NaOMe produced malonate (VI), which was further reduced to diol (VII) by means of NaBH4 in CH2Cl2-MeOH. Treatment of (VII) with tetrabenzyl pyrophosphate in the presence of LDA gave rise to the bis-phosphate ester (VIII). The benzyl groups of (VIII) were then cleaved employing boron trichloride, and the resulting phosphoric acid was purified through an ion-exchange resin in the presence of ammonium bicarbonate to furnish the title tetraammonium salt.
【1】 Boyer, J.L.; Nandanan, E.; Kim, Y.-C.; Adams, M.; Harden, T.K.; Jang, S.-Y.; Jacobson, K.A.; Gallo-Rodriguez, C.; Acyclic analogues of deoxyadenosine 3',5'-bisphosphates as P2Y1 receptor antagonists. J Med Chem 2000, 43, 4, 746. |
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) | 47051 | triethyl methanetricarboxylate | 6279-86-3 | C10H16O6 | 详情 | 详情 |
(II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
(III) | 11646 | triethyl 3-bromo-1,1,1-propanetricarboxylate | C12H19BrO6 | 详情 | 详情 | |
(IV) | 47052 | 2-chloro-N-methyl-9H-purin-6-amine; N-(2-chloro-9H-purin-6-yl)-N-methylamine | C6H6ClN5 | 详情 | 详情 | |
(V) | 47053 | triethyl 3-[2-chloro-6-(methylamino)-9H-purin-9-yl]-1,1,1-propanetricarboxylate | C18H24ClN5O6 | 详情 | 详情 | |
(VI) | 47054 | diethyl 2-[2-[2-chloro-6-(methylamino)-9H-purin-9-yl]ethyl]malonate | C15H20ClN5O4 | 详情 | 详情 | |
(VII) | 47055 | 2-[2-[2-chloro-6-(methylamino)-9H-purin-9-yl]ethyl]-1,3-propanediol | C11H16ClN5O2 | 详情 | 详情 | |
(VIII) | 47056 | dibenzyl 2-([[bis(benzyloxy)phosphoryl]oxy]methyl)-4-[2-chloro-6-(methylamino)-9H-purin-9-yl]butyl phosphate | C39H42ClN5O8P2 | 详情 | 详情 |