2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-chloropurine | 500225-61-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-chloropurine
• 英文别名: [(2R,3S,5R)-5-(2-amino-6-chloropurin-9-yl)-3-benzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 500225-61-6
• 化学式: C₂₄H₂₀ClN₅O₅
• 分子量: 493.906
• InChiKey: UQZGMMYGVBXEAZ-RCCFBDPRSA-N

物化性质

• 沸点：
  733.0±70.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-chloropurine 在 亚硝酸苄基三乙基铵 、 氨 、 乙酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.08h， 生成 克拉屈滨
  参考文献：
  名称：

  Efficient Syntheses of 2-Chloro-2‘-deoxyadenosine (Cladribine) from 2‘-Deoxyguanosine¹

  摘要：

  We report efficient syntheses of the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo), which is the drug of choice against hairy-cell leukemia and other neoplasms, from 2'-deoxyguanosine. Treatment of 3',5'-di-O-acetyl- or benzoyl-2'-deoxyguanosine (1) with 2,4,6-triisopropyl- or 4-methylbenzenesulfonyl chloride gave high yields of the 6-O-arylsulfonyl derivatives 2 or 2%. Deoxychlorination at C6 of 1 also proceeded to give the 2-amino-6-chloropurine derivative 5 in excellent yields. The nonaqueous diazotization/chloro dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2%, and 5 gave the 2-chloropurine derivatives 3, 3'b, and 6, respectively. The selective ammonolysis at C6 (arylsulfonate with 3 or chloride with 6) and accompanying deprotection of the sugar moiety gave CldAdo (64-75% overall yield from 1).

  DOI：

  10.1021/jo020644k
• 作为产物：
  描述：

  3',5'-di-O-benzoyl-2'-deoxyguanosine 在 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以85%的产率得到2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-chloropurine
  参考文献：
  名称：

  Efficient Syntheses of 2-Chloro-2‘-deoxyadenosine (Cladribine) from 2‘-Deoxyguanosine¹

  摘要：

  We report efficient syntheses of the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo), which is the drug of choice against hairy-cell leukemia and other neoplasms, from 2'-deoxyguanosine. Treatment of 3',5'-di-O-acetyl- or benzoyl-2'-deoxyguanosine (1) with 2,4,6-triisopropyl- or 4-methylbenzenesulfonyl chloride gave high yields of the 6-O-arylsulfonyl derivatives 2 or 2%. Deoxychlorination at C6 of 1 also proceeded to give the 2-amino-6-chloropurine derivative 5 in excellent yields. The nonaqueous diazotization/chloro dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2%, and 5 gave the 2-chloropurine derivatives 3, 3'b, and 6, respectively. The selective ammonolysis at C6 (arylsulfonate with 3 or chloride with 6) and accompanying deprotection of the sugar moiety gave CldAdo (64-75% overall yield from 1).

  DOI：

  10.1021/jo020644k

文献信息

• METHOD FOR THE PREPARATION OF 2-HALO-2'-DEOXYADENOSINE COMPOUNDS FROM 2'-DEOXYGUANOSINE
  申请人：Robins Morris J.

  公开号：US20090270604A1

  公开（公告）日：2009-10-29

  The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2′-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2′-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2′-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

  本发明涉及制备2-卤代-6-氨基嘌呤，更具体地说，从2-氨基-6-氧代嘌呤制备临床药物克拉德霉素（2-氯-2'-脱氧腺苷，CldAdo，4），这是针对毛细胞白血病和其他肿瘤的首选药物。2-氨基-6-氧代嘌呤可以从天然存在的2'-脱氧鸟苷中轻松获得。根据本发明的方法，保护的2'-脱氧鸟苷（1）的6-氧代基被转化为6-（取代氧）离去基，或者被转化为6-氯离去基，2-氨基被2-氯代基取代，6-（取代氧）离去基或6-氯离去基被6-氨基取代，或者选择性地用6-氨基取代2,6-二氯取代化合物，并去除保护基。
• Method for the preparation of 2-halo-2'-deoxyadenosine compounds for 2'-deoxyguanosine
  申请人：Robins J. Morris

  公开号：US20070032645A1

  公开（公告）日：2007-02-08

  The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2′-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2′-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2′-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

  本发明涉及一种制备2-卤代-6-氨基嘌呤的方法，更具体地说，是从2-氨基-6-氧代嘌呤制备临床药物克拉德霉素（2-氯-2'-脱氧腺苷，CldAdo，4），这是一种用于治疗毛细胞白血病和其他肿瘤的首选药物。2-氨基-6-氧代嘌呤是从天然存在的2'-脱氧鸟苷中容易得到的。根据本发明的方法，保护的2'-脱氧鸟苷（1）的6-氧代基被转化为6-(取代氧)离去基，或者替代为6-氯离去基，2-氨基被替换为2-氯基，6-(取代氧)离去基或者6-氯离去基被替换为6-氨基或者2,6-二氯取代化合物被选择性地替换为6-氨基，并去除保护基。
• SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
  申请人：Alios Biopharma, Inc.

  公开号：EP3421482A1

  公开（公告）日：2019-01-02

  Disclosed herein are nucleotide analogs of formula (I), methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs, wherein the substituents are as defined in the appended claims.

  本文公开了式(I)的核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷酸类似物治疗疾病和/或诸如HCV感染等病症的方法、 其中取代基如所附权利要求中定义。
• 4'-FLUORO-NUCLEOSIDES, 4'-FLUORO-NUCLEOTIDES AND ANALOGS THEREOF FOR THE TREATMENT OF HCV
  申请人：Janssen BioPharma, Inc.

  公开号：EP3912984A1

  公开（公告）日：2021-11-24

  Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

  本文公开了核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷酸类似物治疗疾病和/或病症（如 HCV 感染）的方法。
• METHOD FOR THE PREPARATION OF 2-HALO-2 -DEOXYADENOSINE COMPOUNDS FROM 2 -DEOXYGUANOSINE
  申请人：Brigham Young University

  公开号：EP1556400B1

  公开（公告）日：2013-05-01