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【结 构 式】

【分子编号】52975

【品名】(2R)-2-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-4,4-diethoxy-1-butanol

【CA登记号】

【 分 子 式 】C14H22ClN5O3

【 分 子 量 】343.81328

【元素组成】C 48.91% H 6.45% Cl 10.31% N 20.37% O 13.96%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXVI)

In a different protection strategy, (diethoxyethyl)malonate (XIX) was obtained by alkylation of diethyl malonate (XVII) with bromoacetaldehyde diethyl acetal (XVIII). Reduction of the ester groups of (XIX) with LiBH4 provided diol (XX). The asymmetric mono-acetate ester (XXI) was generated by enantioselective acylation of the prochiral diol (XX) with vinyl acetate in the presence of lipase PS 30. Reaction of the free hydroxyl of (XXI) with p-toluenesulfonyl chloride afforded tosylate (XXII), which was subsequently condensed with 2-amino-6-chloropurine (I), yielding adduct (XXIII). Conversion of the chloropurine ring of (XXIII) to the target guanine derivative (XXV) was achieved by displacement of the chloro group with benzyl alcohol, with concomitant acetate ester hydrolysis, followed by hydrogenolytic cleavage of the resultant benzyl ether (XXIV). Alternatively, initial acetate ester hydrolysis in (XXIII) gave alcohol (XXVI), which was further subjected to chloro group hydrolysis in the presence of either KOH or tertiary amines to yield (XXV). Conversion of alcohol (XXV) to the target stearate ester (XXVIII) was achieved by treatment with stearoyl chloride (IX) or with the mixed anhydride of stearic acid (XXVII) with pivaloyl chloride or with tosyl chloride.

1 Engelhardt, P.; Hoberg, M.; Zhou, X.-X.; Lindborg, B.; Johansson, N.G. (Medivir AB); Acyclic nucleoside derivs.. EP 0888348; JP 2000504720; JP 2000504721; US 5869493; WO 9730051; WO 9730052 .
2 Synthesis of acyclic nucleoside derivs.. WO 9834917 .
3 Synthesis of acyclic nucleoside derivs.. WO 0008025 .
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) 11644 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine 10310-21-1 C5H4ClN5 详情 详情
(IX) 52961 n-Octadecanoyl chloride; Octadecanoyl Chloride; Stearic acid chloride; Stearoyl chloride 112-76-5 C18H35ClO 详情 详情
(XVII) 16829 Diethyl malonate 105-53-3 C7H12O4 详情 详情
(XVIII) 12113 2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal 2032-35-1 C6H13BrO2 详情 详情
(XIX) 52968 3,3-Diethoxypropane-1,1-dicarboxylic acid diethyl ester; Diethyl 3,3-Diethoxypropane-1,1-dicarboxylate 21339-47-9 C13H24O6 详情 详情
(XX) 52969 2-(2,2-Diethoxyethyl)-1,3-propanediol; 2-Hydroxymethyl-4,4-diethoxybutanol 55387-85-4 C9H20O4 详情 详情
(XXI) 52970 (2R)-4,4-diethoxy-2-(hydroxymethyl)butyl acetate C11H22O5 详情 详情
(XXII) 52971 (2S)-4,4-diethoxy-2-({[(4-methylphenyl)sulfonyl]oxy}methyl)butyl acetate C18H28O7S 详情 详情
(XXIII) 52972 (2R)-2-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-4,4-diethoxybutyl acetate C16H24ClN5O4 详情 详情
(XXIV) 52973 (2R)-2-{[2-amino-6-(benzyloxy)-9H-purin-9-yl]methyl}-4,4-diethoxy-1-butanol C21H29N5O4 详情 详情
(XXV) 52974 2-amino-9-[(2R)-4,4-diethoxy-2-(hydroxymethyl)butyl]-1,9-dihydro-6H-purin-6-one C14H23N5O4 详情 详情
(XXVI) 52975 (2R)-2-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-4,4-diethoxy-1-butanol C14H22ClN5O3 详情 详情
(XXVII) 27095 stearic acid 57-11-4 C18H36O2 详情 详情
(XXVIII) 52976 (2R)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-4,4-diethoxybutyl stearate C32H57N5O5 详情 详情
Extended Information