N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide -Drug Synthesis Database

【结构式】

【分子编号】27921

【品名】N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide

【CA登记号】

【分子式】C₂₅H₄₃N₃O₆

【分子量】481.63304

【元素组成】C 62.35% H 9% N 8.72% O 19.93%

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：(IV)

This compound can be obtained in two different ways: 1) By condensation of 1-beta-D-arabinofuranosylcytosine (I) with palmitic anhydride (II) in hot dioxane. 2) By acylation of cytidine (III) with palmitic anhydride (II) in hot dioxane to yield N4-palmitoylcytidine (IV), which is then isomerized by treatment with POCl3 in ethyl acetate.

参考文献中间体

合成目标

【1】 Ishida, T.; et al.; JP 7626884 .
【2】 Ishida, T.; et al.; JP 7707974 .
【3】 Ishida, T.; et al.; JP 7632573 .
【4】 Akiyama, M.; et al.; The synthesis of new derivatives of 1-beta-D-arabinofuranosylcytosine. Chem Pharm Bull 1978, 26, 3, 981-984.
【5】 Ishida, T.; et al.; JP 7648679 .
【6】 Ishida, T.; et al. (Asahi Chemical Industry Co., Ltd.); N4-Acylarabinonucleosides. DE 2461862 .
【7】 Ishida, T.; et al. (Asahi Chemical Industry Co., Ltd.); N4-Acylarabinonucleosides and the preparation thereof. DE 2426304 .
【8】 Cabanillas, F.; Castaner, J.; Palmitoyl/Stearoyl Ara-C. Drugs Fut 1980, 5, 12, 617.

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)	32709	Cytarabine; Cytosine Beta-D-Arabinofuranoside; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone	147-94-4	C₉H₁₃N₃O₅	详情	详情
(II)	39214	acetic hexadecanoic anhydride		C₁₈H₃₄O₃	详情	详情
(III)	27920	Cytidine; 4-amino-1-((2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone	65-46-3	C₉H₁₃N₃O₅	详情	详情
(IV)	27921	N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₂₅H₄₃N₃O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

4) The acylation of cytidine (VII) with hexadecanoyl anhydride (III) in hot DMF gives N-4-hexadecanoylcytidine (VIII), which is protected with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in pyridine, yielding the 3',5'-cyclic disiloxane (IX). The oxidation of (IX) with pyridinium dichromate in dichloromethane affords the ketonic derivative (X), which is treated with NaCN in ethyl acetate/phosphate buffer to give 2'-C-cyano-N4-hexadecanoyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)cytidine (XI). The reaction of (XI) with phenoxythiocarbonyl chloride and DMAP in triethylamine provides the thiocarbonate (XII), which is reduced with AIBN and tributyltin in refluxing toluene to give the 2'-deoxy compound (VI). Finally, this compound is desilylated with TBAF in acetic acid.

参考文献中间体

合成目标

【1】 Castaner, J.; Hoshi, A.; CS-682. Drugs Fut 1999, 24, 9, 957.
【2】 Kaneko, M.; Hotoda, H.; Shibata, T.; Kobayashi, T.; Mitsuhashi, Y.; Matsuda, A.; Sasaki, T. (Sankyo Co., Ltd.); Pyrimidine nucleoside derivs. having anti-tumor activity, their preparation and use. EP 0536936; JP 1993194497; US 5691319 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	27919	N-[1-[(6aR,8R,9S,9aS)-9-cyano-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₃₈H₆₈N₄O₆Si₂	详情	详情
(VII)	27920	Cytidine; 4-amino-1-((2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone	65-46-3	C₉H₁₃N₃O₅	详情	详情
(VIII)	27916	hexadecanoic anhydride	623-65-4	C₃₂H₆₂O₃	详情	详情
(IX)	27921	N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₂₅H₄₃N₃O₆	详情	详情
(X)	27922	N-[1-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₃₇H₆₉N₃O₇Si₂	详情	详情
(XI)	27923	N-[1-[(6aR,8R,9aR)-2,2,4,4-tetraisopropyl-9-oxotetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₃₇H₆₇N₃O₇Si₂	详情	详情
(XII)	27924	N-[1-[(6aR,8R,9R,9aR)-9-cyano-9-hydroxy-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₃₈H₆₈N₄O₇Si₂	详情	详情
(XIII)	27925	O-[(6aR,8R,9R,9aR)-9-cyano-2,2,4,4-tetraisopropyl-8-[2-oxo-4-(palmitoylamino)-1(2H)-pyrimidinyl]tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-yl] O-phenyl carbonothioate		C₄₅H₇₂N₄O₈SSi₂	详情	详情

Extended Information