Selodenoson, RG-14202, DTI-0009, -Drug Synthesis Database

【结构式】

【药物名称】Selodenoson, RG-14202, DTI-0009

【化学名称】N6-Cyclopentyl-N5'-ethyladenosine-5'-uronamide

【CA登记号】110299-05-3

【分子式】C₁₇H₂₄N₆O₄

【分子量】376.41863

【开发单位】Aderis (Originator), Fujisawa (Licensee)

【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Adenosine A1 Agonists

合成路线1 合成路线2

合成路线1

The title compound is prepared by two methods. Chlorination of 2',3'-O-isopropylideneinosine-5'-uronic acid (I) with SOCl2 in the presence of DMF produces the chloropurine acid chloride (II), which is further converted into the amide (III) upon treatment with ethylamine. Subsequent displacement of the purine 6-chloro group of (III) with cyclopentylamine (IV) furnishes the cyclopentylamino purine (V). Finally, acidic ketal hydrolysis in (IV) gives rise to the target compound.

参考文献中间体

【1】 Olsson, R.A.; Thompson, R.D. (UCB Pharma, Inc.); N-6 Substd.-5'-(N-substd. carboxamido)adenosines as cardiac vasodilators and antihypertensive agents. AU 8544972; EP 0191025; ES 8609359; JP 1986286398; US 5310731; WO 8600310 .

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)	61423	(3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid		C₁₃H₁₄N₄O₆	详情	详情
(II)	61424	(3aR,4S,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbonyl chloride		C₁₃H₁₂Cl₂N₄O₄	详情	详情
(III)	61425	(3aR,4S,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide		C₁₅H₁₈ClN₅O₄	详情	详情
(IV)	28850	cyclopentanamine	1003-03-8	C₅H₁₁N	详情	详情
(V)	61426	(3aR,4S,6R,6aR)-6-[6-(cyclopentylamino)-9H-purin-9-yl]-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide		C₂₀H₂₈N₆O₄	详情	详情

合成路线2

Alternatively, the inosine uronic acid (I) is converted to ethyl ester (II) by sequential treatment with thionyl chloride and then ethanol. Subsequent reaction with acetic anhydride in pyridine gives rise to diacetate (III). Chlorination of the inosine ring of (III) to produce (IV) is accomplished by treatment with phosphoryl chloride in the presence of tetraethylammonium chloride. Displacement of the 6-chloro group of (IV) with cyclopentylamine (V) yields amino purine (VI). Finally, aminolysis of the ester groups of (VI) with ethanolic ethylamine leads to the title compound.

参考文献中间体

【1】 Hamilton, H.W.; Patt, W.C. (Pfizer Inc.); N6-Substd.-5'-oxidized adenosine analogs. EP 0222330; JP 1987111996; US 4738954 .

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)	61423	(3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid		C₁₃H₁₄N₄O₆	详情	详情
(II)	61427	ethyl (3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylate		C₁₅H₁₈N₄O₆	详情	详情
(III)	61428	ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-2-furancarboxylate		C₁₆H₁₈N₄O₈	详情	详情
(IV)	61429	ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(6-chloro-9H-purin-9-yl)tetrahydro-2-furancarboxylate		C₁₆H₁₇ClN₄O₇	详情	详情
(V)	28850	cyclopentanamine	1003-03-8	C₅H₁₁N	详情	详情
(VI)	61430	ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-[6-(cyclopentylamino)-9H-purin-9-yl]tetrahydro-2-furancarboxylate		C₂₁H₂₇N₅O₇	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)