Azidothymidine, Zidovudine, Cpd S, AZT, BW-A509U, AZTEC, Retrovir, -Drug Synthesis Database

【结构式】

【药物名称】Azidothymidine, Zidovudine, Cpd S, AZT, BW-A509U, AZTEC, Retrovir

【化学名称】3'-Azido-3'-deoxythymidine

【CA登记号】30516-87-1

【分子式】C₁₀H₁₃N₅O₄

【分子量】267.24621

【开发单位】GlaxoSmithKline (Originator)

【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Reverse Transcriptase Inhibitors

合成路线1 合成路线2

合成路线1

1) The mesylation of 5'-O-tritylthymidine with mesyl chloride gives the corresponding 3'-O-mesyl derivative (II), which is cyclized by means of potassium phthalimide (III) in hot DMF water, yielding 5'-O-trityl-2,3'-anhydrothymidine (IV). The reaction of (IV) with sodium azide in refluxing DMF - water affords 5'-O-trityl-3'-azido-3'-deoxy thymidine (V), which is finally deprotected with 80% aqueous acetic acid at 100 C.

参考文献中间体

【1】 Glinski, R.P.; et al.; Nucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivatives. J Org Chem 1973, 38, 25, 4299.
【2】 Castaner, J.; Prous, J.; BW-A 509 U. Drugs Fut 1986, 11, 12, 1017.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	12166	1-[(2R,4S,5R)-4-Hydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	C₂₉H₂₈N₂O₅	详情	详情
(II)	12196	(2R,3S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[(trityloxy)methyl]tetrahydro-3-furanyl methanesulfonate	C₃₀H₃₀N₂O₇S	详情	详情
(III)	10926	(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium	C₈H₄KNO₂	详情	详情
(IV)	12168	(1R,9R,10R)-4-Methyl-10-[(trityloxy)methyl]-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-5-one	C₂₉H₂₆N₂O₄	详情	详情
(V)	24469	1-[4-azido-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	C₂₉H₂₇N₅O₄	详情	详情

合成路线2

2) The anhydrization of thymidine (VI) with 2-chloro-1,2-difluorotriethylamine in hot DMF gives 2,3'-anhydrothymidine (VII), which is then treated with lithium azide and NH4Cl in hot DMF.

参考文献中间体

【1】 Glinski, R.P.; et al.; Nucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivatives. J Org Chem 1973, 38, 25, 4299.
【2】 Castaner, J.; Prous, J.; BW-A 509 U. Drugs Fut 1986, 11, 12, 1017.

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)	12161	Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	50-89-5	C₁₀H₁₄N₂O₅	详情	详情
(VII)	24471	(1R,9S,10R)-10-(hydroxymethyl)-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-5-one; 2,3'-Anhydrothymidine; 2,3'-2,3'-Anhydrothimidine		C₁₀H₁₂N₂O₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)