(3S,4S)-4-甲氧基-N-甲基-3-吡咯烷胺 | 252574-01-9

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (3S,4S)-4-甲氧基-N-甲基-3-吡咯烷胺
• 中文别名: (3S,4S)-4-甲氧基-N-甲基-吡咯-3-胺；Voreloxin中间体；Vosaroxin中间体
• 英文名称: (3S,4S)-3-methoxy-4-(N-methylammmonio)pyrrolidinium
• 英文别名: (3S,4S)-3-methoxy-4-methylaminopyrrolidine；(3s,4s)-4-Methoxy-n-methylpyrrolidin-3-amine
• CAS: 252574-01-9
• 化学式: C₆H₁₄N₂O
• 分子量: 130.19
• InChiKey: FHCMZTOUVZUHAP-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  33.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-甲氧基-N-甲基-3-吡咯烷胺 在 sodium hydroxide 、 乙醇 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 48.0h， 生成 白血病孤儿药
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2

  摘要：

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

  DOI：

  10.1021/jm0304966
• 作为产物：
  描述：

  methyl (3R,αS)-3-[N-methyl-N-(α-methylbenzyl)amino]-4-(N'-benzyl-N'-allylamino)butanoate 在 palladium dihydroxide 、 四(三苯基膦)钯 2,2,6,6-四甲基哌啶 、 lithium aluminium tetrahydride 、 正丁基锂 、 氢气 、 silica gel 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、506.66 kPa 条件下， 反应 102.0h， 生成 (3S,4S)-4-甲氧基-N-甲基-3-吡咯烷胺
  参考文献：
  名称：

  通过酰胺化锂共轭物的不对称合成3,4-抗-和3,4-syn-取代的氨基吡咯烷。

  摘要：

  高手性锂酰胺向4-（N-烯丙基-N-苄氨基）丁-2-烯酸甲酯的非对映选择性共轭加成已被用作制备3,4-取代的氨基吡咯烷酮的简单有效方法中的关键步骤。该协议通过β-氨基烯醇官能团在高de和ee方面为抗3和4-3-氨基-4-烷基吡咯烷酮和顺3-氨基4-烷基吡咯烷酮提供了互补和立体选择的途径。该方法学已被用于合成抗-（3S，4S）-和顺-（3R，4S）-3-甲氧基-4-（N-甲基氨基）吡咯烷。

  DOI：

  10.1039/b704932c

文献信息

• [EN] STABLE SNS-595 COMPOSITIONS AND METHODS OF PREPARATION<br/>[FR] COMPOSITIONS STABLES DE SNS-595 ET PROCÉDÉS DE PRÉPARATION
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2011028979A1

  公开（公告）日：2011-03-10

  Methods of preparing substantially pure SNS-595 substance are disclosed. Also provided are compositions comprising SNS-595 substance that are substantially pure and essentially free of visible particles.

  公开了制备基本纯净的SNS-595物质的方法。还提供了含有基本纯净且基本无可见颗粒的SNS-595物质的组合物。
• Lithium amide conjugate addition for the asymmetric synthesis of 3-aminopyrrolidines
  作者：Stephen G. Davies、A. Christopher Garner、Euan C. Goddard、Dennis Kruchinin、Paul M. Roberts、Humberto Rodriguez-Solla、Andrew D. Smith

  DOI：10.1039/b604835h

  日期：——

  Conjugate addition of homochiral lithium amides to methyl 4-(N-benzyl-N-allylamino)but-2-enoate, chemoselective N-deprotection and concomitant cyclisation, followed by enolate functionalisation and deprotection allows access to syn- and anti-3,4-disubstituted aminopyrrolidines in > 98% d.e. and > 98% e.e.

  将同手性锂酰胺加到4-（N-苄基-N-烯丙基氨基）丁-2-烯酸甲酯中，进行化学选择性N-去保护和伴随的环化反应，然后烯醇化功能化和去保护作用，可以得到顺式和反式3,4 -di取代的氨基吡咯烷类化合物，de≥98％，ee≥98％
• [EN] METHOD OF PREPARING (+)-1,4-DIHYDRO-7-[(3S,4S)-3METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ACIDE (+)-1,4-DIHYDRO-7-[(3S,4S)-3-MÉTHOXY-4-(MÉTHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTYRIDINE-3-CARBOXYLIQUE
  申请人：SUNESIS PHARMACEUTICAL INC

  公开号：WO2010078294A1

  公开（公告）日：2010-07-08

  Methods of preparing (+)-1, 4-dihydro-7-[(3S,45)-3-methoxy-4-(methylamino)-1 - pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

  本发明揭示了制备(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的方法。本发明还提供了包含(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的药物组合物，并提供了使用这种组合物进行治疗的方法。
• IGF-1R INHIBITOR
  申请人：Kanda Yutaka

  公开号：US20090054508A1

  公开（公告）日：2009-02-26

  The present invention provides a type I insulin-like growth factor receptor (IGF-1R) inhibitor comprising, as an active ingredient, an indazole derivative represented by Formula (I): wherein R 1 represents —NR 4 R 5 [wherein R 4 represents a hydrogen atom or the like, R 5 represents substituted or unsubstituted lower alkyl, —C(═O)R 6 (wherein R 6 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl or the like), or the like], or the like, and R 2 and R 3 may be the same or different and each represents a hydrogen atom, hydroxy, substituted or unsubstituted lower alkoxy, or the like} or a pharmaceutically acceptable salt thereof, and the like.

  本发明提供了一种I型胰岛素样生长因子受体（IGF-1R）抑制剂，其包含下式（I）所表示的吲唑衍生物作为活性成分：其中，R1表示—NR4R5[其中，R4表示氢原子或类似物，R5表示取代或未取代的低碳基，—C（═O）R6（其中，R6表示取代或未取代的低碳基，取代或未取代的芳基或类似物），或类似物]，或类似物，R2和R3可以相同也可以不同，分别表示氢原子，羟基，取代或未取代的低烷氧基，或类似物}或其药学上可接受的盐等。
• Method of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid
  申请人：Sudhakar Anantha

  公开号：US20100203162A1

  公开（公告）日：2010-08-12

  Methods of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

  本文披露了制备(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的方法。同时，还提供了含有(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的制药组合物，并且还提供了使用这种组合物进行治疗的方法。