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【结 构 式】 
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【分子编号】14432 【品名】[(1R,2R,4S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methanol 【CA登记号】 |
【 分 子 式 】C12H17N5O3 【 分 子 量 】279.29888 【元素组成】C 51.6% H 6.13% N 25.07% O 17.19% |
合成路线1
该中间体在本合成路线中的序号：(LXII)7) [14C]-labeled lobucavir has been synthesized as follows: The reaction of [1R-(1alpha,2beta,3alpha)]-2,3-di(benzyloxymethyl)cyclobutan-1-amine (LVI) with 4,6-dichloropyrimidine-2-amine (XXXIII) by means of triethylamine in acetonitrile gives [1R-(1alpha,2beta,3alpha]-4-[2,3-di(benzyloxymethyl)cyclobutylamino]-6-chloropyrimidine-2-amine (LVII), which is condensed with 4-chlorophenyldiazonium chloride (XXXV) to afford the azo derivative (LVIII). The reduction of (LVIII) with Zn/acetic acid yields the corresponding 2,5-diaminopyrimidine derivative (LIX), which is cyclized with [14C]-labeled triethyl orthoformate to give [8-14C]-[1R-(1alpha,2beta,3alpha)]-9-[2,3-di(benzyloxymethyl) cyclobutyl]-6-chloropurine-2-amine (LX). The reaction of (LX) with sodium methoxide in methanol yields the corresponding 6-O-methylguanine derivative (LXI), which is debenzylated by hydrogenolysis with H2 over Pd(OH)2 in ethanol/cyclohexane affording [8-14C]-[1R-(1alpha,2beta,3alpha)]-9-[2,3-di(hydroxymethyl)cyclobutyl]-6-O-methylguanine (LXII). Finally, this compound is demethylated with aqueous HCl.
| 【1】 Egli, P.; Rinehart, J.K.; Synthesis of [14C]BMS-180194, an antiviral compound. In: Synthesis and Applications of Isotopically Labelled Compounds 1995, 689-91. |
| 【2】 Ireland, C.; Leeson, P.A.; Castaner, J.; Lobucavir. Drugs Fut 1997, 22, 4, 359. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 14404 | 4,6-dichloro-2-pyrimidinamine; 2-Amino-4,6-dichloropyrimidine; 4,6-dichloro-2-pyrimidinylamine | 56-05-3 | C4H3Cl2N3 | 详情 | 详情 |
| (XXXV) | 10197 | 4-Chlorobenzenediazonium chloride | C6H4Cl2N2 | 详情 | 详情 | |
| (LVI) | 14426 | (1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutylamine; (1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutanamine | C20H25NO2 | 详情 | 详情 | |
| (LVII) | 14427 | N(4)-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-2,4-pyrimidinediamine; N-(2-amino-6-chloro-4-pyrimidinyl)-N-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]amine | C24H27ClN4O2 | 详情 | 详情 | |
| (LVIII) | 14428 | N-[2-amino-6-chloro-5-[(E)-2-(4-chlorophenyl)diazenyl]-4-pyrimidinyl]-N-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]amine; N(4)-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-5-[(E)-2-(4-chlorophenyl)diazenyl]-2,4-pyrimidinediamine | C30H30Cl2N6O2 | 详情 | 详情 | |
| (LIX) | 14429 | N-[(E)-2-amino-1-chloroethylidene]-N''-[([(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]amino)methyl]guanidine | C24H32ClN5O2 | 详情 | 详情 | |
| (LX) | 14430 | 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-9H-purin-2-ylamine; 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-9H-purin-2-amine | C25H26ClN5O2 | 详情 | 详情 | |
| (LX) | 45221 | 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-9H-purin-2-amine; 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-chloro-9H-purin-2-ylamine | C25H26ClN5O2 | 详情 | 详情 | |
| (LXI) | 14431 | 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-methoxy-9H-purin-2-amine; 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-methoxy-9H-purin-2-ylamine | C26H29N5O3 | 详情 | 详情 | |
| (LXI) | 45222 | 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-methoxy-9H-purin-2-amine; 9-[(1R,2R,3S)-2,3-bis[(benzyloxy)methyl]cyclobutyl]-6-methoxy-9H-purin-2-ylamine | C26H29N5O3 | 详情 | 详情 | |
| (LXII) | 14432 | [(1R,2R,4S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methanol | C12H17N5O3 | 详情 | 详情 | |
| (LXII) | 45223 | [(1R,2R,4S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methanol | C12H17N5O3 | 详情 | 详情 |