(R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane | 652990-08-4

• 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: (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane
• 英文别名: 2-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethane；N-{2-benzyloxy-5-[(1R)-2-bromo-1-(tert-butyldimethylsilanyloxy)ethyl]phenyl}formamide；N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}formamide；N-[2-benzyloxy-5-((R)-2-bromo-1-(tert-butyldimethylsilanyloxy)ethyl)phenyl]formamide；N-[5-((R)-2-bromo-1-(tert-butyl-dimethyl-silanyloxy)-ethyl)-2-benzyloxy-phenyl]-formamide；[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]formamide；(R)-N-(2-(benzyloxy)-5-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)phenyl)formamide；N-[5-[(1R)-2-bromo-1-[tert-butyl(dimethyl)silyl]oxyethyl]-2-phenylmethoxyphenyl]formamide
• CAS: 652990-08-4
• 化学式: C₂₂H₃₀BrNO₃Si
• 分子量: 464.475
• InChiKey: SFPUYVLZDLLXTQ-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.29
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 在 N-甲基吗啉 、 5%-palladium/activated carbon 、 氢气 、 sodium acetate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 醋酸异丙酯 、 水 、 丁酮 为溶剂， 22.0~90.0 ℃ 、152.0 kPa 条件下， 反应 32.5h， 生成 GSK159797
  参考文献：
  名称：

  Sequential Acetic Acid–Sodium Chloride Treatment to Control Salt Stoichiometry of a Hydrochloride Salt

  摘要：

  The sequential treatment of an intermediate in the synthesis of GSK159797 with a protic acid and sodium chloride was developed to control the stoichiometry of the hydrochloric acid salt of the API. This offered significant advantages over addition of hydrochloric acid, thus avoiding decomposition of an acid-sensitive formamide group. A range of acids were investigated to determine the optimum pK(a) range in which to use the acid. The optimum process, using acetic acid, was performed on >100 kg input scale.

  DOI：

  10.1021/op2003375
• 作为产物：
  描述：

  (R)-N-(2-(苄氧基)-5-(2-溴-1-羟基乙基)苯基)甲酰胺 以68的产率得到(R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane
  参考文献：
  名称：

  Crystalline form of beta2 adrenergic receptor agonist

  摘要：

  本发明提供了一种新的β2肾上腺素能受体激动剂晶体盐形式。本发明还提供了包含该新的β2肾上腺素能受体激动剂晶体盐形式的制药组合物、包含制药组合物的配方、使用晶体盐治疗与β2肾上腺素能受体活性相关的疾病的方法，以及用于制备这种晶体化合物的有用过程。

  公开号：

  US20040248985A1
• 作为试剂：
  描述：

  (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 、 2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethylamine 在 (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 作用下， 以99的产率得到N-{2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl}-(R)-2-tert-butyldimethylsiloxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine
  参考文献：
  名称：

  Crystalline form of beta2 adrenergic receptor agonist

  摘要：

  本发明提供了一种新的β2肾上腺素能受体激动剂晶体盐形式。本发明还提供了包含该新的β2肾上腺素能受体激动剂晶体盐形式的制药组合物、包含制药组合物的配方、使用晶体盐治疗与β2肾上腺素能受体活性相关的疾病的方法，以及用于制备这种晶体化合物的有用过程。

  公开号：

  US20040248985A1

文献信息

• Azabicycloalkane compounds
  申请人：——

  公开号：US20040242622A1

  公开（公告）日：2004-12-02

  This invention provides compounds of formula I: 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both &bgr; 2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

  这项发明提供了式I的化合物： 其中R1、R2、R3、R4、R5、R6和R7如规范中所定义，或其药用可接受盐、溶剂或立体异构体。本发明的化合物具有β2肾上腺素受体激动剂和肌碱受体拮抗剂活性。这些化合物对治疗肺部疾病，如慢性阻塞性肺病和哮喘，是有用的。
• Compounds having beta adrenergic receptor agonist and muscarinic receptor antagonist activity
  申请人：Mammen Mathai

  公开号：US20060035933A1

  公开（公告）日：2006-02-16

  This invention provides compounds of formula I: wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8a , R 8b , W, a, b, c and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β 2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

  这项发明提供了式I的化合物：其中R1、R2、R4、R5、R6、R7、R8a、R8b、W、a、b、c和m如规范中所定义，或其药学上可接受的盐、溶剂或立体异构体。本发明的化合物具有β2肾上腺素受体激动剂和肌碱受体拮抗剂活性。因此，这些化合物预计可用作治疗肺部疾病，如慢性阻塞性肺病和哮喘的治疗剂。
• [EN] FORMAMIDE DERIVATIVES USEFUL AS ADRENOCEPTOR<br/>[FR] DERIVES DE FORMAMIDE UTILES COMME RECEPTEURS ADRENERGIQUES
  申请人：PFIZER LTD

  公开号：WO2005092840A1

  公开（公告）日：2005-10-06

  The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  该发明涉及公式（1）的化合物，以及用于制备、用于制备的中间体、含有和用途的过程。根据本发明的化合物在许多疾病、紊乱和情况中都有用，特别是在炎症、过敏和呼吸系统疾病、紊乱和情况中。
• Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
  申请人：Colson Pierre-Jean

  公开号：US20070249675A1

  公开（公告）日：2007-10-25

  This invention relates to compounds of formula I: wherein R 1 and R 2 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions and combinations comprising such compounds, processes and intermediates for preparing such compounds, and methods of using such compound to, for example, treat pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

  本发明涉及式I的化合物：其中R1和R2如规范中定义，或其药用可接受的盐或溶剂或立体异构体。该发明还涉及包含这类化合物的药物组合物和配方，用于制备这类化合物的过程和中间体，以及使用这类化合物治疗肺部疾病，如慢性阻塞性肺病和哮喘等方法。
• [EN] COMPOUNDS HAVING BETA-AGONIST ACTIVITY<br/>[FR] COMPOSES PRESENTANT UNE ACTIVITE BETA-AGONISTE
  申请人：PFIZER LTD

  公开号：WO2005092841A1

  公开（公告）日：2005-10-06

  The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  本发明涉及化合物的公式（1）以及用于制备、制备中间体、含有和使用这些衍生物的过程。根据本发明的化合物在许多疾病、紊乱和情况中有用，特别是炎症性、过敏性和呼吸道疾病、紊乱和情况。