2-[3-(2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]-phenyl}-2-hydroxyethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide | 921598-22-3

• 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: 2-[3-(2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]-phenyl}-2-hydroxyethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide
• 英文别名: 2-(3-{2-[((2R)-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}-2-hydroxyethyl)amino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]-acetamide；2-[3-[2-[[(2R)-2-hydroxy-2-[3-(methanesulfonamido)-4-phenylmethoxyphenyl]ethyl]amino]-2-methylpropyl]phenyl]-N-[[3-(4-hydroxyphenyl)phenyl]methyl]acetamide
• CAS: 921598-22-3
• 化学式: C₄₁H₄₅N₃O₆S
• 分子量: 707.891
• InChiKey: SJDGCFWXSJBQDR-LHEWISCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[3-(2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]-phenyl}-2-hydroxyethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide 在 5% palladium over charcoal 氢气 作用下， 以 乙二醇 为溶剂， 40.0 ℃ 、551.59 kPa 条件下， 反应 45.0h， 生成 (R)-2-(3-{2-[2-(4-benzyloxy-3-methanesulfonamidophenyl)-2-hydroxyethylamino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide hemifumarate
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF SULFONAMIDE DERIVATIVES
  [FR] PROCEDE POUR LA PREPARATION DE DERIVES DE SULFONAMIDE

  摘要：

  公开号：

  WO2007010356A3
• 作为产物：
  描述：

  N-[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methane sulfonamide 在 potassium carbonate 、 triethylamine tris(hydrogen fluoride) 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 butironitrile 、 水 、 乙腈 为溶剂， 反应 69.17h， 生成 2-[3-(2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]-phenyl}-2-hydroxyethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide
  参考文献：
  名称：

  Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist

  摘要：

  The development of a practical, scalable route to PF-00610355 (8) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26. TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a. On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API (8) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.

  DOI：

  10.1021/op2002408

文献信息

• Inhibitors of nedd8-activating enzyme
  申请人：IP Gesellschaft für Management mbH

  公开号：EP2764866A1

  公开（公告）日：2014-08-13

  The invention relates to an administration unit comprising crystalline form I of (1 S,2S,4R)-4-[(6-[(1R,2S)-5-chloro-2methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]-2-hydroxycyclopentyl}methyl sulfamate (I-216) hydrochloride salt and to a packaging comprising the administration unit according to the invention.

  该发明涉及一种包含晶型I的(1S,2S,4R)-4-[(6-[(1R,2S)-5-氯-2甲氧基-2,3-二氢-1H-茚-1-基]氨基}嘧啶-4-基)氧基]-2-羟基环戊基}甲基磺酰胺(I-216)盐酸盐的管理单元，以及包括该管理单元的包装。
• [EN] INTERMEDIATE AND PROCESS FOR THE PREPARATION OF A SULFONAMIDE DERIVATIVE<br/>[FR] INTERMÉDIAIRE ET PROCÉDÉ DE PRÉPARATION D'UN DÉRIVÉ SULFONAMIDE
  申请人：PFIZER LTD

  公开号：WO2013021309A1

  公开（公告）日：2013-02-14

  The invention relates to a crystalline form of 2-chloro-N-2-[3-(2-[(4'-hydroxybiphenyl-3- yl)methyl]amino}-2-oxoethyl)phenyl]-1,1-dimethylethyl}acetamide, a process for preparing the same and its use in the preparation of the 2 agonist N-[(4'-hydroxybiphenyl-3- yl)methyl]-2-(3-2-[((2R)-2-hydroxy-2-4-hydroxy-3- [(methylsulfonyl)amino]phenyl}ethyl)amino]-2-methylpropyl} phenyl)acetamide which is useful in the treatment of respiratory diseases.

  该发明涉及一种结晶形式的2-氯-N-2-[3-(2-[(4'-羟基联苯-3-基)甲基]氨基}-2-氧乙基)苯基]-1,1-二甲基乙基}乙酰胺，以及其制备方法和在制备β2激动剂N-[(4'-羟基联苯-3-基)甲基]-2-(3-2-[((2R)-2-羟基-2-4-羟基-3-[(甲磺酰)氨基]苯基}乙基)氨基]-2-甲基丙基}苯基)乙酰胺中的应用，该激动剂在呼吸系统疾病治疗中有用。
• Process for the Preparation of Sulfonamide Derivatives
  申请人：Gladwell Iain Robert

  公开号：US20080193988A1

  公开（公告）日：2008-08-14

  The invention relates to a process for the preparation of compounds of formula (I) wherein Q 1 is a group selected from formulae (II) & (III) and a group *-NR 6 -Q 2 -A or, if appropriate, their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof, as well as intermediates used in said process.

  本发明涉及一种制备式（I）化合物的过程，其中Q1是从式（II）和（III）中选择的基团以及基团*-NR6-Q2-A，或者在适当的情况下，它们的药学上可接受的盐和/或异构体、互变异构体、溶剂化物或同位素变体，以及用于该过程的中间体。
• Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate <b>5</b>
  作者：Stéphane Content、Thomas Dupont、Nicolas M. Fédou、Julian D. Smith、Steven J. R. Twiddle

  DOI：10.1021/op300341n

  日期：2013.2.15

  Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled beta-2 adrenoreceptor agonist PF-610355. Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed in context of the synthesis of S. The optimized process employed to manufacture 140 kg of 5 is described, and was shown to have superior metrics to the preliminary commercial route.