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【结 构 式】

【药物名称】MRS-2286

【化学名称】2-[2-[2-Chloro-6-(methylamino)purin-9-yl]ethyl]propane-1,3-diol bis(monophosphate) tetraammonium salt

【CA登记号】

【 分 子 式 】C11H30ClN9O8P2

【 分 子 量 】513.81785

【开发单位】National Institutes of Health (Originator), Universidad de Buenos Aires (Originator), University of North Carolina (Originator)

【药理作用】PHARMACOLOGICAL TOOLS, P2Y1 Antagonists

合成路线1

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
Extended Information