4-(4-hydroxy-5-nitropentyl)benzoic acid methyl ester | 229471-26-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(4-hydroxy-5-nitropentyl)benzoic acid methyl ester
• 英文别名: 1-nitro-5-(4-methoxycarbonylphenyl)-2-pentanol；Methyl 4-(4-hydroxy-5-nitropentyl)benzoate
• CAS: 229471-26-5
• 化学式: C₁₃H₁₇NO₅
• 分子量: 267.282
• InChiKey: MFZAMXNVSALMKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxy-5-nitropentyl)benzoic acid methyl ester 在 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 (2S)-2-[[4-[3-(2,4-二氨基-7H-吡咯并[4,5-e]嘧啶-5-基)丙基]苯甲酰基]氨基]戊烷二酸
  参考文献：
  名称：

  Exploitation of a new route to fused pyrroles: Synthesis of TNP-351, homo-MTA and 5-arylpyrrolo[2,3-]pyrimidines

  摘要：

  We have developed a new methodology for the construction of pyrrolo[2,3-d]pyrimidines that involves Michael addition of 2,6-diamino-4(3 (H) under bar)-pyrimidinone or 2,4,6-triaminopyrimidines to nitroolefins, followed by a Nef reaction of the resulting adduct to form an intermediate aldehyde that spontaneously cyclizes to the fused pyrrole ring, This methodology has been exploited in a new synthesis of TNP-351, and for the first reported preparation of homo-MTA and of a series of 5-arylpyrrolo[2,3-(d) under bar]pyrimidines. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00677-2
• 作为产物：
  描述：

  4-(4-羟基-1-丁炔基)苯甲酸甲酯 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0~38.0 ℃ 、344.74 kPa 条件下， 反应 69.0h， 生成 4-(4-hydroxy-5-nitropentyl)benzoic acid methyl ester
  参考文献：
  名称：

  一种新型高效合成吡咯并[2,3-d]嘧啶抗癌药：Alimta（LY231514，MTA），均阿利姆他，TNP-351和一些芳基5-取代的吡咯并[2,3-d]嘧啶。

  摘要：

  已经通过一种新方法制备了Alimta以及均Alimta，Alimta的非桥接类似物以及TNP-351，该方法涉及将适当的1-硝基烯烃与2,6-二氨基-3H-嘧啶-4-酮进行迈克尔加成反应。或2,4,6-三氨基嘧啶，然后进行Nef反应，生成伯硝基迈克尔加合物。所得醛与嘧啶6-氨基的自发分子内环化反应产生相应的吡咯并[2,3-d]嘧啶。用相同的方法由上述嘧啶和硝基苯乙烯制备一系列以前未知的5-芳基吡咯并[2，3-d]嘧啶。已经发现，可以通过在含乙酸铵的乙酸中对芳基醛，硝基甲烷和6-氨基嘧啶的混合物进行超声处理而一步制备中间体伯硝基迈克尔加合物。

  DOI：

  10.1021/jo030248h

文献信息

• [EN] PROCESS FOR THE PREPARATION OF PYRROLO[2,3-D]PYRIMIDINES<br/>[FR] PROCEDE DE PREPARATION DE PYRROLO[2,3-D]PYRIMIDINES
  申请人：UNIV PRINCETON

  公开号：WO2000011004A1

  公开（公告）日：2000-03-02

  4(3H)-X-7H-Pyrrolo[2,3-d]pyrimidines in which X is =O or =NH are prepared by (i) treating a 6-amino-4(3H)-X-pyrimidine with a unsubstituted or substituted 1-nitroalk-1-ene to yield a 6-amino-4(3H)-X-pyrimidine which is substituted in the 5-position by a 1-nitroalk-2-yl group; (ii) converting the 5-(1-nitroalk-2-yl)-6-amino-4(3H)-X-pyrimidine to the corresponding 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyrimidine; and (iii) removing the elements of water from the 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyrimidine to effect cyclization. A typical embodiment involves treating 2,6-diamino-4(3H)-pyrimidone with 1-nitro-4-(4-ethoxycarbonylphenyl)-I-butene to yield 1-nitro-2-(2,6-diamino 4(3H)-oxopyrimidin-5-yl)-4-(4-ethoxycarbonylphenyl)butane which is then treated sequentially with base and acid, without isolation of the intermediate aldehyde, to form 4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, a valuable known chemical intermediate for the preparation of N-[4-2-(2-hydroxy-4-amino-7H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl}benzoyl]glutamic acid.

  本发明涉及一种制备4(3H)-X-7H-吡咯并[2,3-d]嘧啶的方法，其中X = O或= NH，包括以下步骤：(i)用非取代或取代的1-硝基烯烃处理6-氨基-4(3H)-X-嘧啶，得到在5-位上被1-硝基烷基取代的6-氨基-4(3H)-X-嘧啶；(ii)将5-(1-硝基烷基-2-基)-6-氨基-4(3H)-X-嘧啶转化为相应的5-(1-氧代烷基-2-基)-6-氨基-4(3H)-X-嘧啶；(iii)从5-(1-氧代烷基-2-基)-6-氨基-4(3H)-X-嘧啶中除去水分以进行环化。典型实施例包括用1-硝基-4-(4-乙氧羰基苯基)-1-丁烯处理2,6-二氨基-4(3H)-嘧啶，得到1-硝基-2-(2,6-二氨基4(3H)-氧代嘧啶-5-基)-4-(4-乙氧羰基苯基)丁烷，然后依次用碱和酸处理而不分离中间体醛，形成4-[2-(2-氨基-4(3H)-氧代-7H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酸，这是制备N-[4-2-(2-羟基-4-氨基-7H-吡咯并[2,3-d]-嘧啶-5-基)乙基}苯甲酰]谷氨酸的有价值的已知化学中间体。
• PROCESS FOR THE PREPARATION OF PYRROLO[2,3-D]PYRIMIDINES
  申请人：The Trustees of Princeton University

  公开号：EP1105396A1

  公开（公告）日：2001-06-13
• US6066732A
  申请人：——

  公开号：US6066732A

  公开（公告）日：2000-05-23
• A New and Efficient Synthesis of Pyrrolo[2,3-<i>d</i>]pyrimidine Anticancer Agents:  Alimta (LY231514, MTA), Homo-Alimta, TNP-351, and Some Aryl 5-Substituted Pyrrolo[2,3-<i>d</i>]pyrimidines
  作者：Edward C. Taylor、Bin Liu

  DOI：10.1021/jo030248h

  日期：2003.12.1

  primary nitro Michael adduct. Spontaneous intramolecular cyclization of the resulting aldehyde with the pyrimidine 6-amino group yields the corresponding pyrrolo[2,3-d]pyrimidine. A series of previously unknown 5-arylpyrrolo[2,3-d]pyrimidines was prepared by the same methodology from the above pyrimidines and nitrostyrenes. It has been found that the intermediate primary nitro Michael adduct can be prepared

  已经通过一种新方法制备了Alimta以及均Alimta，Alimta的非桥接类似物以及TNP-351，该方法涉及将适当的1-硝基烯烃与2,6-二氨基-3H-嘧啶-4-酮进行迈克尔加成反应。或2,4,6-三氨基嘧啶，然后进行Nef反应，生成伯硝基迈克尔加合物。所得醛与嘧啶6-氨基的自发分子内环化反应产生相应的吡咯并[2,3-d]嘧啶。用相同的方法由上述嘧啶和硝基苯乙烯制备一系列以前未知的5-芳基吡咯并[2，3-d]嘧啶。已经发现，可以通过在含乙酸铵的乙酸中对芳基醛，硝基甲烷和6-氨基嘧啶的混合物进行超声处理而一步制备中间体伯硝基迈克尔加合物。
• Exploitation of a new route to fused pyrroles: Synthesis of TNP-351, homo-MTA and 5-arylpyrrolo[2,3-]pyrimidines
  作者：Edward C. Taylor、Bin Liu

  DOI：10.1016/s0040-4039(99)00677-2

  日期：1999.5

  We have developed a new methodology for the construction of pyrrolo[2,3-d]pyrimidines that involves Michael addition of 2,6-diamino-4(3 (H) under bar)-pyrimidinone or 2,4,6-triaminopyrimidines to nitroolefins, followed by a Nef reaction of the resulting adduct to form an intermediate aldehyde that spontaneously cyclizes to the fused pyrrole ring, This methodology has been exploited in a new synthesis of TNP-351, and for the first reported preparation of homo-MTA and of a series of 5-arylpyrrolo[2,3-(d) under bar]pyrimidines. (C) 1999 Elsevier Science Ltd. All rights reserved.