7-<4-acetoxy-3-(acetoxymethyl)butyl>-2-amino-6-chloro-9H-purine | 97845-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 7-<4-acetoxy-3-(acetoxymethyl)butyl>-2-amino-6-chloro-9H-purine
• 英文别名: 7-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine；7-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine；7-[4-acetoxy-3-(acetoxymethyl)butyl]-2-amino-6-chloropurine；1,3-Propanediol, 2-[2-(2-amino-6-chloro-7H-purin-7-yl)ethyl]-, 1,3-diacetate；[2-(acetyloxymethyl)-4-(2-amino-6-chloropurin-7-yl)butyl] acetate
• CAS: 97845-61-9
• 化学式: C₁₄H₁₈ClN₅O₄
• 分子量: 355.781
• InChiKey: WEHQKUAQWVHZQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 7-<4-acetoxy-3-(acetoxymethyl)butyl>-2-amino-6-chloro-9H-purine
  参考文献：
  名称：

  Convenient syntheses of 9-[4-hydroxy-3-(hydroxymethyl)butyl]guanine (penciclovir) and 9-[4-acetoxy-3-(acetoxymethyl)butyl]-2-amino-9H-purine (famciclovir)

  摘要：

  Guanine 11 was converted, in a one pot reaction, into 2-amino-6-[(4-chlorophenyl)sulfanyl]purine 9a in 88% isolated yield. 4-Acetoxy-3-(acetoxymethyl)butanol 23 was prepared from 2-chloroethanol in five steps and in 46% overall yield. The mesylate ester of compound 23 reacted with 9a in the presence of potassium carbonate with a high degree of regioselectivity (89%) to give the N-9 alkylated product 26 which was isolated in 80% yield. Acidic hydrolysis of the latter compound 26 gave penciclovir 4 in virtually quantitative yield. Penciclovir 4 and famciclovir 5 were prepared from 2-amino-6-[(4-chlorophenyl)sulfanyl]puri 9a in four and five steps, respectively, by procedures involving initial alkylation with 1,2-dibromoethane. The overall yields obtained were 65 and ca. 60%, respectively. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00169-6

文献信息

• [EN] A PROCESS FOR THE PREPARATION OF 2-ACETOXYMETHYL-4 HALO-BUT-1-YL ACETATES<br/>[FR] PROCEDE DE PREPARATION D'ACETATES DE 2-ACETOXYMETHYL-4 HALO-BUT-1-YLE
  申请人：RECORDATI CHEM PHARM

  公开号：WO2004007418A1

  公开（公告）日：2004-01-22

  A process for the preparation of 2- acetoxymethyl-4-halo-but-l-yl acetates (I) in which X is chlorine or bromine, which are useful intermediates for the preparation of antiviral medicaments such as Penciclovir and Famciclovir, comprising the opening of 3-hydroxymethyl-tetrahydrofuran (V) in the presence of an acylating agent and a Lewis acid selected from magnesium bromide and samarium triiodide.

  一种制备2-乙酰氧甲基-4-卤代-丁-1-酯（I）的方法，其中X为氯或溴，这些化合物是用于制备抗病毒药物如Penciclovir和Famciclovir的有用中间体，包括在存在酰化剂和从镁溴化物和三碘化钐中选择的Lewis酸的情况下打开3-羟甲基-四氢呋喃（V）。
• [EN] 2-AMINO-9-(2-SUBSTITUTED ETHYL)PURINES AND PREPARING METHODS FOR 9-[4-ACETOXY-3-(ACETOXYMETHYL)BUT-1-YL]- 2- AMINOPURINE USING THE SAME<br/>[FR] 2-AMINO-9-(2-SUBSTITUE ETHYL)PURINES ET PROCEDES DE PREPARATION DE 9-[4-ACETOXY-3-(ACETOXYMETHYL)BUT-1-YL]- 2- AMINOPURINE AU MOYEN DE CELLES-CI
  申请人：KYUNGDONG PHARM CO LTD

  公开号：WO2004110343A2

  公开（公告）日：2004-12-23

  The present invention relates to a new compound of 2-amino-9-(2-substituted ethyl)purine and an effective method for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurin (famciclovir) using the same. The 2-amino-9-(2-substituted ethyl)purine according to the invention is represented by the following formula (II'): (Formula II') wherein R is a hydroxy, halogen, mesyloxy or tosyloxy group. The inventive method for the preparation of famciclovir comprises the steps of halogenating 2-amino-9-(2-substituted ethyl)purine to give 2-amino-9-(2-halogenoethyl)purine, and reacting the halogenated compound with diethylmalonate. The inventive preparation method allows famciclovir, a purine derivative drug with effective antiviral activity, to be prepared in a high selectivity of 100% in a pure form by using the inventive new compound of 2-amino-9-(2-substituted ethyl)purine. In addition, the inventive method allows the utilization of relatively mild reaction conditions, and thus, has high industrial process efficiency.

  本发明涉及一种新的2-氨基-9-(2-取代乙基)嘌呤化合物以及利用该化合物制备9-[4-乙酰氧基-3-(乙酰氧甲基)丁-1-基]-2-氨基嘌呤（法昔洛韦）的有效方法。根据本发明，2-氨基-9-(2-取代乙基)嘌呤的化合物由以下公式（II'）表示：（公式II'）其中R是羟基，卤素，甲烷磺氧基或对甲苯磺氧基。本发明的制备法包括以下步骤：卤代2-氨基-9-(2-取代乙基)嘌呤，得到2-氨基-9-(2-卤代乙基)嘌呤，然后将卤代化合物与乙酰丙酮酸二乙酯反应。本发明的制备方法允许使用新的2-氨基-9-(2-取代乙基)嘌呤化合物以高达100％的纯度制备具有有效抗病毒活性的嘌呤衍生物药物法昔洛韦。此外，本发明的方法允许使用相对温和的反应条件，因此具有高的工业过程效率。
• Process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine
  申请人：Lee Byoung-suk

  公开号：US20050222413A1

  公开（公告）日：2005-10-06

  Disclosed is a process for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine (called Famciclovir), a drug of purine derivatives having antiviral activity. This process comprises reacting 2-aminopurine with 2-acetoxymethyl-4-bromobut-1-yl-acetate in the presence of thallium (1) ethoxide to give the desired compound. According to this process, the desired compound can be prepared in very high selectivity and purity under mild reaction conditions.

  本发明公开了一种制备9-[4-乙酰氧基-3-(乙酰氧甲基)丁-1-基]-2-氨基嘌呤（称为法昔洛韦）的嘌呤衍生物药物的方法，具有抗病毒活性。该方法包括在铊（1）乙氧化物存在下，将2-氨基嘌呤与2-乙酰氧甲基-4-溴丁-1-基-乙酸酯反应，以得到所需化合物。根据该方法，在温和的反应条件下，所需化合物可以高选择性和高纯度地制备。
• 2-Amino-9-(2-substituted ethyl)purines and preparing methods for 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine using the same
  申请人：Lee Byoung-Suk

  公开号：US20060258862A1

  公开（公告）日：2006-11-16

  The present invention relates to a new compound of 2-amino-9-(2-substituted ethyl)purine and an effective method for preparing 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurin (famciclovir) using the same. The 2-amino-9-(2-substituted ethyl)purine according to the invention is represented by the following formula (II′): (Formula II′) wherein R is a hydroxy, halogen, mesyloxy or tosyloxy group. The inventive method for the preparation of famciclovir comprises the steps of halogenating 2-amino-9-(2-substituted ethyl)purine to give 2-amino-9-(2-halogenoethyl)purine, and reacting the halogenated compound with diethylmalonate. The inventive preparation method allows famciclovir, a purine derivative drug with effective antiviral activity, to be prepared in a high selectivity of 100% in a pure form by using the inventive new compound of 2-amino-9-(2-substituted ethyl)purine. In addition, the inventive method allows the utilization of relatively mild reaction conditions, and thus, has high industrial process efficiency.

  本发明涉及一种2-氨基-9-(2-取代乙基)嘌呤的新化合物及利用该化合物制备9-[4-乙酰氧基-3-(乙酰氧甲基)丁-1-基]-2-氨基嘌呤(famciclovir)的有效方法。本发明所述的2-氨基-9-(2-取代乙基)嘌呤由以下式子(II')表示：(式子II')，其中R是羟基、卤素、mesyloxy或tosyloxy基团。本发明的famciclovir制备方法包括以下步骤：卤化2-氨基-9-(2-取代乙基)嘌呤以得到2-氨基-9-(2-卤代乙基)嘌呤，然后将卤代化合物与乙酰丙酮酸二乙酯反应。本发明的制备方法可利用2-氨基-9-(2-取代乙基)嘌呤这种新化合物高选择性地制备出具有有效抗病毒活性的嘌呤衍生物药物famciclovir，纯度可达100%。此外，本发明的方法可利用相对温和的反应条件，因此具有较高的工业过程效率。
• Process for the preparation of purine derivatives
  申请人：Beecham Group plc

  公开号：US20010004668A1

  公开（公告）日：2001-06-21

  The present invention provides a process for the synthesis of penciclovir and famciclovir by 9-substituting 2-amino-6-chloropurine (ACP) with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy moiety (i.e. to form a guanine) or hydrogen (to form a 2-aminopurine), respectively.

  本发明提供了一种合成喷昔洛韦和泛昔洛韦的工艺，该工艺通过将 2-氨基-6-氯嘌呤 (ACP) 与适当的侧链前体进行 9-取代，然后将 6-氯基分别转化为羟基（即形成鸟嘌呤）或氢（形成 2-氨基嘌呤）。