西他列汀杂质 | 382638-00-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 西他列汀杂质
• 英文名称: (S)-3-tert-Butoxycarbonylamino-4-methanesulfonyloxybutanoic acid methyl ester
• 英文别名: methyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfonyloxybutanoate
• CAS: 382638-00-8
• 化学式: C₁₁H₂₁NO₇S
• 分子量: 311.356
• InChiKey: RILFJXIJIKZHQA-QMMMGPOBSA-N

物化性质

• 沸点：
  474.0±40.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (S)-3-(BOC-氨基)-4-羟基丁酸甲酯	methyl (3S)-3-(tert-butoxycarbonylamino)-4-hydroxybutanoate	136703-59-8	C10H19NO5	233.265
  (S)-n-boc-3-氨基-4-羟基丁酸	(S)-3-((tert-Butoxycarbonyl)amino)-4-hydroxybutanoic acid	83345-44-2	C9H17NO5	219.238
  Boc-L-天冬氨酸 4-甲酯	(S)-2-t-butoxycarbonylaminosuccinic acid 4-methyl ester	59768-74-0	C10H17NO6	247.248
  ——	benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoate	79069-16-2	C16H23NO5	309.362

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl (3S)-4-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate	1028260-16-3	C10H20N2O4	232.28

反应信息

• 作为反应物：
  描述：

  西他列汀杂质 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Design, synthesis and SAR of novel ethylenediamine and phenylenediamine derivatives as factor Xa inhibitors

  摘要：

  We previously reported on a series of cyclohexanediamine derivatives as highly potent factor Xa inhibitors. Herein, we describe the modification of the spacer moiety to discover an alternative scaffold. Ethylenediamine derivatives possessing a substituent at the C1 position in S configuration and phenylenediamine derivatives possessing a substituent at the C5 position demonstrated moderate to strong anti-fXa activity. Further SAR studies led to the identification of compound 30h which showed both good in vitro activity (fXa IC50 = 2.2 nM, PTCT2 = 3.9 mu M) and in vivo antithrombotic efficacy. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.132
• 作为产物：
  描述：

  benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 西他列汀杂质
  参考文献：
  名称：

  Design, synthesis and SAR of novel ethylenediamine and phenylenediamine derivatives as factor Xa inhibitors

  摘要：

  We previously reported on a series of cyclohexanediamine derivatives as highly potent factor Xa inhibitors. Herein, we describe the modification of the spacer moiety to discover an alternative scaffold. Ethylenediamine derivatives possessing a substituent at the C1 position in S configuration and phenylenediamine derivatives possessing a substituent at the C5 position demonstrated moderate to strong anti-fXa activity. Further SAR studies led to the identification of compound 30h which showed both good in vitro activity (fXa IC50 = 2.2 nM, PTCT2 = 3.9 mu M) and in vivo antithrombotic efficacy. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.132

文献信息

• Function-Oriented Synthesis of Liponucleoside Antibiotics
  作者：Tetsuya Tanino、Mayumi Yamaguchi、Akira Matsuda、Satoshi Ichikawa

  DOI：10.1002/ejoc.201400140

  日期：2014.3

  Function-oriented synthesis of a class of liponucleoside antibiotics was investigated through rational simplification guided by previous structure–activity relationship studies of caprazamycins and muraymycins to address the issue associated with their molecular complexity. A lactam-fused isoxazolidine scaffold was designed, and a diverse set of lactam-fused isoxazolidines derivatives were constructed

  以功能为导向的一类脂核苷类抗生素的合成是通过合理简化的方法进行研究的，该研究以先前对卡普拉霉素和壁霉素的构效关系研究为指导，以解决与其分子复杂性相关的问题。设计了内酰胺稠合异恶唑烷支架，并通过烯基硝酮的分子内 1,3-偶极环加成构建了一组多样化的内酰胺稠合异恶唑烷衍生物。几种类似物对一系列革兰氏阳性耐药细菌病原体表现出中等活性。
• From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: The discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis
  作者：Joseph B. Santella、Daniel S. Gardner、Wenqing Yao、Chongsheng Shi、Prabhakar Reddy、Andrew J. Tebben、George V. DeLucca、Dean A. Wacker、Paul S. Watson、Patricia K. Welch、Eric A. Wadman、Paul Davies、Kimberly A. Solomon、Dani M. Graden、Swamy Yeleswaram、Sandhya Mandlekar、Ilona Kariv、Carl P. Decicco、Soo S. Ko、Percy H. Carter、John V. Duncia

  DOI：10.1016/j.bmcl.2007.11.067

  日期：2008.1

  Conformational analysis of trans-1,2-disubstituted cyclohexane CCR3 antagonist 2 revealed that the cyclohexane linker could be replaced by an acyclic syn-alpha-methyl-beta-hydroxypropyl linker. Synthesis and biological evaluation of mono- and disubstituted propyl linkers support this conformational correlation. It was also found that the alpha-methyl group to the urea lowered protein binding and that

  反式1,2-二取代的环己烷CCR3拮抗剂2的构象分析表明，环己烷接头可被无环的顺式α-甲基-β-羟丙基接头取代。单取代和双取代丙基连接基的合成和生物学评估支持这种构象相关性。还发现与尿素的α-甲基降低了蛋白结合，而β-羟基降低了对CYP2D6的亲和力。从头算计算表明，α-甲基基团控制着分子内三个关键功能的空间取向。具有嗜酸性粒细胞趋化性IC（50）= 38 pM的α-甲基-β-羟丙基尿素31被选择进入临床治疗哮喘的研究。
• [EN] NEW HETEROCYCLIC AMIDE COMPOUNDS USEFUL FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS: PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX COMPOSES AMIDES HETEROCYCLIQUES UTILISES POUR LE TRAITEMENT D'AFFECTIONS INFLAMMATOIRES ET ALLERGIQUES; PROCEDE PERMETTANT DE LES FABRIQUER ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2004022536A1

  公开（公告）日：2004-03-18

  The present invention relates to novel heterocyclic compounds that inhibit phosphodiesterase type 4 (PDE 4). The compounds are useful for treating inflammatory conditions, diseases of the central nervous systems and insulin resistant diabetes.

  本发明涉及一种新型杂环化合物，可抑制磷酸二酯酶4型（PDE 4）。这些化合物可用于治疗炎症性疾病、中枢神经系统疾病和胰岛素抵抗性糖尿病。
• Process for Preparation of Nonnatural Amino Acid and Intermediate Thereof
  申请人：Ishii Yutaka

  公开号：US20070208180A1

  公开（公告）日：2007-09-06

  A process for the preparation of a nonnatural amino acid represented by the following formula (C): which is characterized by reacting a compound represented by the following formula (A1), a compound represented by the following formula (A2) and a compound represented by the following formula (A3) (step 1): to form a compound represented by the following formula (B): and then subjecting the compound (B) to deprotection of protective groups of carboxyl groups and to decarboxylation (wherein X 1 and X 2 are a leaving group, R 1 is an aromatic group, an unsaturated heterocyclic group, or R 6 CO group, R 2 and R 3 are a protected carboxyl group, R 4 is a protected amino group, R 5 is hydrogen atom, an aliphatic hydrocarbon group, an aromatic group, or a heterocyclic group, R 6 is an aromatic group or an unsaturated heterocyclic group, etc., and p, q and r are an integer of 0 to 10).

  一种制备以下式(C)所表示的非天然氨基酸的方法，其特征在于将以下式(A1)、以下式(A2)和以下式(A3)所表示的化合物进行反应（步骤1）：以形成以下式(B)所表示的化合物，然后将化合物(B)进行羧基保护基的去保护和脱羧作用（其中X1和X2是离去基，R1是芳香基、不饱和杂环基或R6CO基，R2和R3是保护羧基，R4是保护氨基，R5是氢原子、脂肪烃基、芳香基或杂环基，R6是芳香基或不饱和杂环基等，p、q和r是0到10的整数）。
• PROCESS FOR PRODUCTION OF NONNATURAL AMINO ACIDS AND INTERMEDIATES THEREFOR
  申请人：DAISO CO., LTD.

  公开号：EP1739077A1

  公开（公告）日：2007-01-03

  A process for the preparation of a nonnatural amino acid represented by the following formula (C): which is characterized by reacting a compound represented by the following formula (A1), a compound represented by the following formula (A2) and a compound represented by the following formula (A3) (step 1): to form a compound represented by the following formula (B): and then subjecting the compound (B) to deprotection of protective groups of carboxyl groups and to decarboxylation (wherein X1 and X2 are a leaving group, R1 is an aromatic group, an unsaturated heterocyclic group, or R6CO group, R2 and R3 are a protected carboxyl group, R4 is a protected amino group, R5 is hydrogen atom, an aliphatic hydrocarbon group, an aromatic group, or a heterocyclic group, R6 is an aromatic group or an unsaturated heterocyclic group, etc., and p, q and r are an integer of 0 to 10).

  一种制备下式(C)所代表的非天然氨基酸的工艺： 其特征在于将下式（A1）代表的化合物、下式（A2）代表的化合物和下式（A3）代表的化合物反应（步骤 1）： 生成下式（B）代表的化合物： 然后将化合物（B）进行羧基保护基团的脱保护和脱羧（其中 X1 和 X2 是离去基团，R1 是芳香基团、不饱和杂环基团或 R6CO 基团，R2 和 R3 是受保护的羧基，R4 是受保护的氨基，R5 是氢原子、脂肪烃基团、芳香基团或杂环基团，R6 是芳香基团或不饱和杂环基团等、以及 p、q 和 r 为 0 至 10 的整数）。