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【结 构 式】

【分子编号】56696

【品名】{(2S,4S)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl}methyl benzoate

【CA登记号】

【 分 子 式 】C17H17N3O6

【 分 子 量 】359.3386

【元素组成】C 56.82% H 4.77% N 11.69% O 26.71%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VII)

Displacement of the chlorine atom of (I) with potassium benzoate in boiling DMF afforded benzoate ester (II). The hydroxymethyl group of (II) was subsequently oxidized to carboxylic acid (III) employing pyridinium dichromate. Conversion of acid (III) to the corresponding mixed anhydride with ethyl chloroformate, followed by Baeyer-Villiger oxidation with m-chloroperbenzoic acid, gave rise to the m-chlorobenzoyloxy dioxolane (IV). This was then coupled to cytosine (V) following a previously reported procedure to produce adduct (VI) as a cis/trans mixture. After acetylation with Ac2O, the desired cis-isomer (VII) was isolated by flash chromatography. The title compound was finally obtained by basic hydrolysis (VII).

1 Belleau, B.; Dixit, D.; Nguyen-Ba, N. (Shire BioChem Inc.); 2-Substd.-4-substd.-1,3-dioxolanes, synthesis and use thereof. EP 0337713 .
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) 56692 [(2S,4R)-2-(chloromethyl)-1,3-dioxolan-4-yl]methanol C5H9ClO3 详情 详情
(II) 56693 [(2S,4R)-4-(hydroxymethyl)-1,3-dioxolan-2-yl]methyl benzoate C12H14O5 详情 详情
(III) 25844 (2S,4S)-2-[(benzoyloxy)methyl]-1,3-dioxolane-4-carboxylic acid C12H12O6 详情 详情
(IV) 56694 (2S)-2-[(benzoyloxy)methyl]-1,3-dioxolan-4-yl 3-chlorobenzoate C18H15ClO6 详情 详情
(V) 12706 Cytosine; 4-Amino-2(1H)-pyrimidinone 71-30-7 C4H5N3O 详情 详情
(VI) 56695 {(2S)-4-[4-amino-2-oxo-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl}methyl benzoate C15H15N3O5 详情 详情
(VII) 56696 {(2S,4S)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl}methyl benzoate C17H17N3O6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

In a related procedure, 1,6-anhydro-L-gulose (IX) was obtained from L-gulose (VIII) by treatment with 0.5 N HCl. Oxidative cleavage of (IX) by NaIO4, followed by reduction of the aldehyde groups with NaBH4, led to the dioxolane triol (X), which was further protected as the isopropylidene ketal (XI). Benzoylation of the free hydroxyl of (XI), followed by acidic hydrolysis of the acetonide group, furnished the benzoate diol (XII). Then, oxidation of the vicinal diol moiety of (XII), by means of RuO2 in the presence of NaIO4, afforded carboxylic acid (III). Oxidative decarboxylation of acid (III) with lead tetraacetate produced the key acetoxy dioxolane (XIII). This was coupled with the silylated N-acetylcytosine (XIV) in the presence of trimethylsilyl triflate to yield a mixture of anomers, which were separated by column chromatography. Final hydrolysis of the desired isomer (VII) was then performed by treatment with methanolic ammonia.

1 Kim, H.O.; et al.; Potent anti-HIV and anti-HBV activities of (-)-L-beta-dioxolane-C and (+)-L-beta-dioxolane-T and their asymmetric syntheses. Tetrahedron Lett 1992, 33, 46, 6899.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(III) 25844 (2S,4S)-2-[(benzoyloxy)methyl]-1,3-dioxolane-4-carboxylic acid C12H12O6 详情 详情
(VII) 56696 {(2S,4S)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl}methyl benzoate C17H17N3O6 详情 详情
(VIII) 36947 (3S,4S,5S,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetrol C6H12O6 详情 详情
(IX) 25839 (1S,2S,3S,4S,5S)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol C6H10O5 详情 详情
(X) 56697 (1R)-1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-1,2-ethanediol C6H12O5 详情 详情
(XI) 56698   C9H16O5 详情 详情
(XII) 56699 {(2S,4S)-4-[(1R)-1,2-dihydroxyethyl]-1,3-dioxolan-2-yl}methyl benzoate C13H16O6 详情 详情
(XIII) 25845 [(2S)-4-(acetoxy)-1,3-dioxolan-2-yl]methyl benzoate C13H14O6 详情 详情
(XIV) 56700 N-{2-[(trimethylsilyl)oxy]-4-pyrimidinyl}acetamide C9H15N3O2Si 详情 详情
Extended Information