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【结 构 式】

【分子编号】18955

【品名】diethyl (2R,5S)-5-[(2-amino-6-chloro-9H-purin-9-yl)methyl]tetrahydro-2-furanylphosphonate

【CA登记号】

【 分 子 式 】C14H21ClN5O4P

【 分 子 量 】389.778502

【元素组成】C 43.14% H 5.43% Cl 9.1% N 17.97% O 16.42% P 7.95%

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:(VII)

(S)-5-(Hydroxymethyl)tetrahydrofuran-2-one (I) was converted into bromide (II) by reaction with CBr4 and PPh3. Subsequent reduction of the lactone with DIBAL-H in toluene at -78 C, followed by acetylation of the resulting lactol (III) with Ac2O and pyridine, afforded acetate (IV) as a 1:1 mixture of isomers cis and trans. The phosphonate group was then introduced by a TiCl4-catalyzed Arbuzov reaction with triethyl phosphite at low temperature, to give a mixture of geometric isomers, from which the desired cis compound (V) was isolated by column chromatography. Condensation of this bromide with 2-amino-6-chloropurine (VI) in the presence of Cs2CO3 in DMF gave (VII). The phosphonate ester was hydrolyzed by treatment with excess Me3SiBr to produce an intermediate trimethylsilyl ester, and then the target compound was obtained by simultaneous hydrolysis of the silyl ester to phosphonic acid and the 6-chloropurine group to guanine in boiling water, followed by conversion to the corresponding ammonium salt with NH4OH.

1 Chan, L.; et al.; Identification of novel nucleotide phosphonate analogs with potent anti-HCMV activity. 215th ACS Natl Meet (March 29 1998, Dallas) 1998, Abst MEDI 034.
2 Kong, L.C.C.; Dionne, G.; Quimpere, M.; Brown, W.L.; Nguyen-Ba, N.; Anti-viral cpds.. US 5789394 .
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) 46090 (5R)-5-(hydroxymethyl)dihydro-2(3H)-furanone C5H8O3 详情 详情
(II) 18943 (5S)-5-(bromomethyl)dihydro-2(3H)-furanone C5H7BrO2 详情 详情
(III) 18944 (5S)-5-(bromomethyl)tetrahydro-2-furanol C5H9BrO2 详情 详情
(IV) 18945 (5S)-5-(bromomethyl)tetrahydro-2-furanyl acetate C7H11BrO3 详情 详情
(V) 18953 diethyl (2R,5S)-5-(bromomethyl)tetrahydro-2-furanylphosphonate C9H18BrO4P 详情 详情
(VI) 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
(VII) 18955 diethyl (2R,5S)-5-[(2-amino-6-chloro-9H-purin-9-yl)methyl]tetrahydro-2-furanylphosphonate C14H21ClN5O4P 详情 详情
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