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【结 构 式】 
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【分子编号】18703 【品名】(3R,4S,5R)-2-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol 【CA登记号】 |
【 分 子 式 】C11H14ClN5O5 【 分 子 量 】331.71556 【元素组成】C 39.83% H 4.25% Cl 10.69% N 21.11% O 24.12% |
合成路线1
该中间体在本合成路线中的序号：(III)Reaction of dichloropurine (I) with O-methylhydroxylamine hydrochloride and N-ethyldiisopropylamine in dioxan at 50 C yielded the N-methoxy derivative (II). Subsequent treatment with a catalytic amount of NaOMe in methanol at room temperature provided a mixture of 2-chloro-N-methoxyadenosine (III) and monoacetate (IV), which were separated by flash chromatography. Treatment of monoacetate (IV) with alpha-acetoxyisobutyryl bromide (V) in acetonitrile at low temperature yielded bromide (VI), which on further treatment with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) gave the didehydrocompound (VII). Finally, reaction with NaOMe in methanol at 50 C provided the title compound.
| 【1】 Knutsen, L.; Olsen, U.B.; Roberts, S.M.; Varley, D.R.; Bowler, A.N. (Novo Nordisk A/S); Novel N-alkoxyadenine derivs. acting as cytokine inhibitors. WO 9801459 . |
| 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) | 18701 | (2R,3R,4R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H16Cl2N4O7 | 详情 | 详情 | |
| (II) | 18702 | (2R,3R,4R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]tetrahydro-3-furanyl acetate | C17H20ClN5O8 | 详情 | 详情 | |
| (III) | 18703 | (3R,4S,5R)-2-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C11H14ClN5O5 | 详情 | 详情 | |
| (IV) | 18704 | [(2R,3S,4R)-5-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl acetate | C13H16ClN5O6 | 详情 | 详情 | |
| (V) | 12806 | 2-bromo-1,1-dimethyl-2-oxoethyl acetate; alpha-Acetoxy-isobutyryl bromide | 40635-67-4 | C6H9BrO3 | 详情 | 详情 |
| (VI) | 18706 | [(2R,3S,4S)-4-(acetoxy)-3-bromo-5-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]tetrahydro-2-furanyl]methyl acetate | C15H17BrClN5O6 | 详情 | 详情 | |
| (VII) | 18707 | [(4R)-4-(acetoxy)-5-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]-4,5-dihydro-2-furanyl]methyl acetate | C15H16ClN5O6 | 详情 | 详情 |