{(2S,4S)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl}methyl benzoate -Drug Synthesis Database

【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 合成路线2

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).

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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	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