Ladakamycin(formerly), Azacitidine, U-18496, NSC-102816, Vidaza, Mylosar, -Drug Synthesis Database

【结构式】

【药物名称】Ladakamycin(formerly), Azacitidine, U-18496, NSC-102816, Vidaza, Mylosar

【化学名称】5-Azacytidine
　　　　　　4-Amino-1-(beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one
　　　　　　1-(beta-D-Ribofuranosyl)-5-azacytosine

【CA登记号】320-67-2

【分子式】C₈H₁₂N₄O₅

【分子量】244.20864

【开发单位】Pharmion (Orphan Drug), Pfizer (Originator), Pharmion (Licensee)

【药理作用】Myelodysplastic Syndrome Therapy, Oncolytic Drugs, DNA Methyltransferase Inhibitors

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6

合成路线1

参考文献中间体

【1】 Niedballa U.VorbrueggenH.1974. Synthesis ofnucleosides13.General synthesis of N-glycosides V.Synthesis of 5-azacytidinesJ Org Chem,39 t 3672 - 3673

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	11626	N-(Trimethylsilyl)-4-[(trimethylsilyl)oxy]-1,3,5-triazin-2-amine; N-(Trimethylsilyl)-N-[4-[(trimethylsilyl)oxy]-1,3,5-triazin-2-yl]amine		C₉H₂₀N₄OSi₂	详情	详情
(VIII)	66143	2-acetoxy-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate	70832-64-3	C₂₈H₂₄O₉	详情	详情
(IX)	66144	(2S,3S,4R)-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-2,3,4-triyl tribenzoate2,3,4-triyl tribenzoate		C₂₈H₂₂N₄O₈	详情	详情

合成路线2

参考文献中间体

【1】 Ionescu D．Blumberg!P.2004, S)rnthesis 0{ 5-azacytidine via nIiHylation of uacyosine US Pat Appl Publ. US 2004186283

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	66145	5-Azacytosine;2-Amino-4-hydroxy-1,3,5-triazine;4-Amino-1,3,5-triazin-2-one	C₃H₄N₄O	详情	详情
(XI)	66146	4-acetyltetrahydrofuran-2,3,5-triyl triacetate	C₁₃H₁₈O₉	详情	详情
(XII)	66147		C₄H₉F₃SiO₃S	详情	详情
(XIII)	66148	(2S,3S,4R)-5-(2-oxo-4-((trimethylsilyl)amino)-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-2,3,4-triyl tribenzoate	C₃₁H₃₀N₄O₈Si	详情	详情

合成路线3

参考文献中间体

【1】 Gaubert G,Gosselin G,Eriksson S,et al.2001. Unnatunl enantiomers of 5-azacyidine analogs: syntheses and enz)rrMtic properties* Nucleasid Nucleotid Nucl Acid, 20(4～7)1 837 --840

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	11626	N-(Trimethylsilyl)-4-[(trimethylsilyl)oxy]-1,3,5-triazin-2-amine; N-(Trimethylsilyl)-N-[4-[(trimethylsilyl)oxy]-1,3,5-triazin-2-yl]amine		C₉H₂₀N₄OSi₂	详情	详情
(VIII)	66143	2-acetoxy-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate	70832-64-3	C₂₈H₂₄O₉	详情	详情

合成路线4

参考文献中间体

【1】 Gaubert G, Mathe C,Imbach J-L, et aL 2000. Umatural enantiomersof 5-azacytidine analogs, syntheses and enzynuc properties.EurJ htled Chem, 35 (11)1 1011~1019

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	66145	5-Azacytosine;2-Amino-4-hydroxy-1,3,5-triazine;4-Amino-1,3,5-triazin-2-one	C₃H₄N₄O	详情	详情
(XIV)	66149	(4S,5R)-2-acetoxy-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate	C₂₈H₂₄O₉	详情	详情
(XV)	66150	(3S,4S,5R)-4-acetoxy-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)-2-((benzoyloxy)methyl)tetrahydrofuran-3-yl benzoate	C₂₄H₂₂N₄O₈	详情	详情

合成路线5

参考文献中间体

【1】 Abbasi MM, El-Wassinu MT, Osman FH, et aL 1987. Silylatiorrmediated oxidation of 2,2'-anhydro-5,6-dihydro-5-azacytidine*J Prakt Chem, 329 (2): 209 - 216

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVI)	66151	(5aS,7S,8aS)-2-amino-7-(hydroxymethyl)-5a,7,8,8a-tetrahydro-4H-furo[2',3':4,5]oxazolo[3,2-a][1,3,5]triazin-8-yl acetate hydrochloride	C₁₀H₁₅ClN₄O₅	详情	详情
(XVII)	66152	2-amino-7-(hydroxymethyl)-5a,7,8,8a-tetrahydro-4H-furo[2',3':4,5]oxazolo[3,2-a][1,3,5]triazin-8-ol hydrochloride	C₈H₁₃ClN₄O₄	详情	详情
(XVIII)	66153	4-amino-1-((3R,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5,6-dihydro-1,3,5-triazin-2(1H)-one	C₈H₁₄N₄O₅	详情	详情

合成路线6

The reaction of 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (I) with dry HCl in ether-acetic anhydride gives 1-chloro-2,3,5-tri-O-acetyl-beta-D-ribofuranose (II), which by reaction with silver isocyanate in dry xylene is converted into 2,3,5-tri-O-acetyl-beta-D-ribofuranosylisocyanate (III). The reaction of (III) with 2-methylisourea (IV) in dry CHCl3 affords 1-(2,3,5-tri-O-acetyl-3-D-ribofuranosyl)-4-methylisobiuret (V), which is cyclized by reaction with ethyl orthoformate at 135 C yielding 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4-methoxy-2-oxo-1,2-dihydro-1,3,5-triazine (VI). Finally, this compound is treated with ammonia in dry methanol.

参考文献中间体

【1】 Sorm, F.; Piskala, A.; Nucleic acid components and their analogues. LI. Synthesis of 1-glycosyl derivatives of 5-azauracil and 5-azacytosine. Coll Czech Chem Commun 1964, 29, 2060-76.
【2】 Von Hoff, D.D.; Azacitidine. Drugs Fut 1980, 5, 8, 392.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	12304	N-[(3R)-9-(2-cyanoethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide		C₂₁H₂₀FN₃O₂S	详情	详情
(I)	33835	(2R,3R,4R,5S)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-3-furanyl acetate	13035-61-5	C₁₃H₁₈O₉	详情	详情
(II)	39189	(2R,3S,4R,5S)-4-(acetoxy)-2-[(acetoxy)methyl]-5-chlorotetrahydro-3-furanyl acetate		C₁₁H₁₅ClO₇	详情	详情
(III)	39190	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-isocyanatotetrahydro-3-furanyl acetate		C₁₂H₁₅NO₈	详情	详情
(IV)	26657	O-methyl isourea; [Amino(imino)methoxy]methane	52328-05-9	C₂H₆N₂O	详情	详情
(V)	39191	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[([[(E)-amino(methoxy)methylidene]amino]carbonyl)amino]tetrahydro-3-furanyl acetate		C₁₄H₂₁N₃O₉	详情	详情
(VI)	39192	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[4-methoxy-2-oxo-1,3,5-triazin-1(2H)-yl]tetrahydro-3-furanyl acetate		C₁₅H₁₉N₃O₉	详情	详情

Extended Information