2-(1,3-benzodioxol-5-yl)-2-bromoacetic acid | 188670-18-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 2-(1,3-benzodioxol-5-yl)-2-bromoacetic acid
• 英文别名: 2-(1,3-benzodioxol-5-yl)-2-bromoacetate；2-bromo-3,4-benzodioxoleacetic acid
• CAS: 188670-18-0
• 化学式: C₉H₇BrO₄
• 分子量: 259.056
• InChiKey: VUKAHVFPXFJSQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1,3-benzodioxol-5-yl)-2-bromoacetic acid 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.75h， 生成
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process

  摘要：

  The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.

  DOI：

  10.1021/op050102f
• 作为产物：
  描述：

  3,4-(亚甲二氧基)苦杏仁酸 在 氢溴酸 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 4.0h， 生成 2-(1,3-benzodioxol-5-yl)-2-bromoacetic acid
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process

  摘要：

  The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.

  DOI：

  10.1021/op050102f

文献信息

• Indole derivatives useful in therapy
  申请人：Pfizer Inc.

  公开号：US06211223B1

  公开（公告）日：2001-04-03

  The invention provides S-(+)-3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonylamino]-2-oxoethyl}-1-methyl-1H-indole-6-carboxylic acid, which is substantially free from its (R)-(−)-enantiomer, and pharmaceutically acceptable derivatives thereof. The compounds are useful in the treatment of inter alia acute renal failure, restenosis and pulmonary hypertension.

  这项发明提供了S-（+）-3- 1-（1,3-苯并二氧杂环戊-5-基）-2-[(2-甲氧基-4-甲基苯基)磺酰氨]-2-氧乙基}-1-甲基-1H-吲哚-6-羧酸，该化合物基本上不含其（R）-（-）-对映体，以及其药学上可接受的衍生物。这些化合物在治疗急性肾衰竭、再狭窄和肺动脉高压等方面是有用的。
• The Design and Synthesis of a Novel, Orally Active, Selective ETA Antagonist
  作者：David J. Rawson、Kevin N. Dack、Roger P. Dickinson、Kim James、Clive Long、Don Walker

  DOI：10.1007/s00044-004-0021-y

  日期：2004.4

  potency and pharmacokinetic properties of an indole-based series of endothelin antagonists have been optimised using in vitro, in silico and in vivo methods. Compound 8 is oxidised in vivo to the active metabolite 7 and has been highlighted as an orally active agent suitable for further profiling. A synthesis of the active enantiomer of the lead compound (8a) and its metabolite (7a) has been developed

  已使用体外、计算机和体内方法优化了基于吲哚的系列内皮素拮抗剂的效力和药代动力学特性。化合物 8 在体内被氧化为活性代谢物 7，并被强调为适合进一步分析的口服活性剂。开发了先导化合物 (8a) 及其代谢物 (7a) 的活性对映异构体的合成方法，并介绍了 8a 的药代动力学和药理学特征。
• [EN] INDOLE DERIVATIVE USEFUL AS ENDOTHELIN RECEPTOR ANTAGONIST<br/>[FR] DERIVE INDOLIQUE UTILE COMME ANTAGONISTE DE RECEPTEUR D'ENDOTHELINE
  申请人：PFIZER LIMITED

  公开号：WO1999020623A1

  公开（公告）日：1999-04-29

  (EN) The invention provides S-(+)-3- 1-(1,3-benzodioxol -5-yl)-2-[ (2-methoxy-4- methylphenyl)sulfonylamino] -2-oxoethyl }-1-methyl -1$i(H)-indole- 6-carboxylic acid, represented by formula (a), which is substantially free from its (R)-(-)-enantiomer, and pharmaceutically acceptable derivatives thereof. The compound is useful in the treatment of $i(inter alia) acute renal failure, restenosis and pulmonary hypertension.(FR) L'invention concerne un acide S-(+)-3- 1,3-benzodioxol -5-yl)-2-[ (2-méthoxy-4- méthylphényl)sulfonylamino] -2-oxoéthyl }-1-méthyl -1$i(H)-indole- 6 carboxylique représenté par la formule (a) qui est sensiblement exempt de son (R)-(-)-énantiomère et ses dérivés pharmaceutiquement acceptables. Les composés sont utiles dans le traitement notamment d'insuffisance rénale aiguë, de resténose et d'hypertension pulmonaire.

  该发明提供了由式(a)表示的S-(+)-3- 1-(1,3-苯并二氧杂环-5-基)-2-[ (2-甲氧基-4-甲基苯基)磺酰胺]-2-氧代乙基 }-1-甲基-1$i(H)-吲哚-6-羧酸，其基本上不含其(R)-(-)-对映体及其药学可接受的衍生物。该化合物在治疗急性肾功能衰竭、再狭窄和肺动脉高压等方面具有用途。
• Racemisation-free synthesis of chiral acylsulfonamides
  作者：David Ellis

  DOI：10.1016/s0957-4166(01)00259-2

  日期：2001.7

  The development and application of a synthesis of acylsulfonamide A avoiding racemisation of the labile benzylic stereogenic centre is described. (C) 2001 Elsevier Science Ltd. All rights reserved.
• The design and synthesis of a novel series of indole derived selective ETA antagonists
  作者：David J Rawson、Kevin N Dack、Roger P Dickinson、Kim James

  DOI：10.1016/s0960-894x(01)00660-6

  日期：2002.1

  Conformational constraint has been used as the key design element in the identification of a series of potent and selective ETA antagonists. The most potent antagonist, 32, (ETA IC50 = 0.55 nM) is 722-fold selective over the ETB receptor, as measured by binding experiments. (C) 2002 Elsevier Science Ltd. All rights reserved.