多佐胺-2-1 | 133359-80-5

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 多佐胺-2-1
• 中文别名: (S)-3-(2-噻吩基硫基)丁酸；(S)-3-(2-噻酚硫基)-丁酸；(3S)-3-(2-噻吩硫代)丁酸
• 英文名称: (S)-3-(2-thienylthio)butyric acid
• 英文别名: (S)-3-(thien-2-ylthio)butyric acid；(3S)-3-(2-thienylthio)butyric acid；(S)-3-(Thiophen-2-ylthio)butanoic acid；(3S)-3-thiophen-2-ylsulfanylbutanoic acid
• CAS: 133359-80-5
• 化学式: C₈H₁₀O₂S₂
• 分子量: 202.298
• InChiKey: SIFFRIHCTBGQTC-LURJTMIESA-N

物化性质

• 沸点：
  354.6±22.0 °C(Predicted)
• 密度：
  1.30

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  90.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  多佐胺-2-1 在 氯磺酸 、 ammonium hydroxide 、 sodium tungstate 、 lithium aluminium tetrahydride 、 dimethyl sulfide borane 、 硫酸 、 双氧水 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 64.5h， 生成 多佐胺-2-6
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013
• 作为产物：
  描述：

  (S)-3-(噻吩-2-基硫代)丁酸甲酯 在 盐酸 作用下， 以 水 为溶剂， 反应 3.0h， 以45 g的产率得到多佐胺-2-1
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013

文献信息

• Process for obtaining 4-hydroxy-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-7,7-dioxide and its enantiomers, and applications thereof
  申请人：Ragactives, S.L.

  公开号：EP2128161A1

  公开（公告）日：2009-12-02

  The invention relates to a process for obtaining cis-4-hydroxy-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-7,7-dioxide, its enantiomers or mixtures thereof, by reduction of 5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-4-one-7,7-dioxide with a reducing agent which generates hydride ions. The obtained compounds are useful as intermediates in the synthesis of chiral active ingredients.

  该发明涉及一种通过用产生氢化物离子的还原剂还原5,6-二氢-6-甲基-4H-噻吩[2,3-b]噻吩吡喃-4-酮-7,7-二氧化物，从而获得顺式-4-羟基-6-甲基-5,6-二氢-4H-噻吩[2,3-b]噻吩吡喃-7,7-二氧化物，其对映体或其混合物的过程。所得化合物在手性活性成分合成中作为中间体有用。
• Process for the preparation of 6-substituted-4-oxo-thieno [2,3b]thiopyran-2-sulfonic acid
  申请人：SANDOZ AG

  公开号：EP1918293A1

  公开（公告）日：2008-05-07

  The present invention relates to one-pot process for the preparation of 6-substituted-4-oxo-thieno[2,3b]thiopyran-2-sulfonic acid of formula (I), which comprises, reacting 2-thienylthiol with alkenyl acid in the presence of an aromatic hydrocarbon solvent and a base, cyclization of the resulting compound and further reacting with an acid anhydride and sulfuric acid to get the desired compound of formula (I). The compound of formula (I) is the key intermediate in the preparation of (S,S)-5,6-dihydro-4-alkyylamino-6-substituted-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide and analogs thereof.

  本发明涉及一种一锅法制备6-取代-4-氧代噻吩[2,3b]噻吩-2-磺酸(I)的方法，包括在芳香烃溶剂和碱的存在下，将2-噻吩硫醇与烯酸反应，得到所需的化合物后，进行环化反应，然后与酸酐和硫酸进一步反应，得到式(I)的目标化合物。式(I)的化合物是制备(S,S)-5,6-二氢-4-烷基氨基-6-取代-4H-噻吩[2,3-b]噻吩-2-磺酰胺-7,7-二氧化物及其类似物的关键中间体。
• Synthesis of (S)-3-(thien-2-ylthio)butyric acid analogs
  申请人：Merck & Co., Inc.

  公开号：US04968815A1

  公开（公告）日：1990-11-06

  (S)-3-(thien-2-ylthio)butyric acid analogs are intermediates in the synthesis of the chiral (S,S)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfon amide-7,7-dioxide and analogs thereof, topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension and glaucoma. They are prepared by condensation of 2-mercaptothiophene and (R)-(+)-.beta.-methyl-.beta.-propiolactone or an analog thereof.

  (S)-3-(噻吩-2-基硫基)丁酸类似物是手性(S,S)-5,6-二氢-4-乙基氨基-6-甲基-4H-噻吩[2,3-b]硫杂吡喃-2-磺酰胺-7,7-二氧化物及其类似物的合成中间体，是局部有效的碳酸酐酶抑制剂，可用于治疗眼压和青光眼。它们通过2-巯基噻吩和(R)-(+)-β-甲基-β-丙内酯或其类似物的缩合反应制备。
• (S)-alkyl 3-(thien-2-ylthio) butyrate and analogs and synthesis thereof
  申请人：MERCK & CO. INC.

  公开号：EP0453195A1

  公开（公告）日：1991-10-23

  (S)-Alkyl 3-(thien-2-ylthio)butyrate and analogs are intermediates in the synthesis of the chiral (S,S)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide and analogs thereof, topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension and glaucoma.

  (S)-3-(噻吩-2-硫基)丁酸烷基酯及其类似物是合成手性(S,S)-5,6-二氢-4-乙氨基-6-甲基-4H-噻吩并[2,3-b]噻喃-2-磺酰胺-7,7-二氧化物及其类似物的中间体，这些类似物是局部有效的碳酸酐酶抑制剂，可用于治疗眼压过高和青光眼。
• β-butyrolactone as a chiral building block in organic synthesis: A convenient synthesis of MK-0507 keto sulfone
  作者：Orin Tempkin、Thomas J. Blacklock、J. Andrew Burke、Maria Anastasia

  DOI：10.1016/0957-4166(96)00350-3

  日期：1996.9

  The nucleophilic ring opening of (R)-beta-butyrolactone 2 with 2-thiophenethiolate is the key step in a straightforward stereospecific synthesis of keto sulfone 1, a precursor to carbonic anhydrase inhibitor MK-0507. Copyright (C) 1996 Elsevier Science Ltd