thiophene-2-carboxylic- acid | 61714-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: thiophene-2-carboxylic- acid
• 英文别名: 2-thiophenecarboxylic-<14C-carbonyl> acid；2-thiophene-[14C]carboxylic acid；Thiophen-2-<14C>-carbonsaeure；2-Thenoic-α¹⁴C-acid；α-14C-Thiophen-2-carbonsaeure；2-Thiophenecarboxylic acid,[carboxyl-14c]；thiophene-2-carboxylic acid
• CAS: 61714-13-4
• 化学式: C₅H₄O₂S
• 分子量: 130.141
• InChiKey: QERYCTSHXKAMIS-RHRFEJLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  thiophene-2-carboxylic- acid 在 草酰氯 作用下， 以 甲苯 为溶剂， 生成 2-thiophene <14C>-carbonyl chloride
  参考文献：
  名称：

  盐酸度洛西汀的不对称合成，一种血清素和去甲肾上腺素的混合摄取抑制剂，及其 C-14 标记的同位素

  摘要：

  盐酸度洛西汀 (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride) 的两种 14 C-同位素异构体，一种有效的混合血清素/去甲肾上腺素摄取抑制剂已通过不对称方法制备合成。钯催化 2-噻吩酰氯 (3c)（或其 [羰基- 14 C] 同位素异构体 3d）与乙烯基三正丁基锡烷的交叉偶联，然后加入 HCl，得到关键的前手性中间体氯酮（ 5a,b) 在适当的氧氮杂硼烷催化剂（14a 或 b）存在下用硼烷进行手性还原，得到 5-氯代醇（7a）及其 14 C 标记的对应物 7b 或类似的 R-氯代醇（6）。通过与 NaI/丙酮反应活化 7a,b，然后相应的碘醇与甲胺反应产生倒数第二个氨基醇 (8a,b)。与 NaH 形成醇盐，然后与 1-氟萘反应产生度洛西汀或其 14 C-标记的同位素异构体 9。或者，6

  DOI：

  10.1002/jlcr.2580360303
• 作为产物：
  描述：

  2-噻吩基锂 、 二氧化碳-14C 以 四氢呋喃 为溶剂， 以97%的产率得到thiophene-2-carboxylic- acid
  参考文献：
  名称：

  Synthesis of carbon‐14 labelled (3‐{[(Z)‐5‐chloro‐2,3‐dihydro‐3‐(hydroxy‐2‐thienylmethylene)‐2‐oxo‐1 H ‐indol‐1‐yle]carbonylamino}propyl)trimethylammonium chloride, a potential cartilage‐targeted antirheumatic drug

  摘要：

  A [C-14]-labelled form of (3-{[(Z)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H-indol-1-yle]carbonylamino}propyl)trimethylammonium chloride, a potential cartilage-targeted antirheumatic drug, was required for pharmacokinetic studies. This compound, labelled with [C-14] located in the C-3 methylene position, was prepared in four steps starting from N-[3-(dimethylamino)propyl]-5-chloro-2,3-dihydro-2-oxo-1H-indole-1-carboxamide and 2-thiophene-[C-14]carbonyl chloride, previously synthesized by a two-step sequence from barium [C-14]-carbonate and 2-thienyllithium. The desired product was obtained with a specific activity of 359 MBq/mmol (9.7 mCi/mmol). The overall radiochemical yield was 50% based on barium [C-14]-carbonate.

  DOI：

  10.1002/(sici)1099-1344(20000315)43:3<297::aid-jlcr317>3.0.co;2-#

文献信息

• An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers
  作者：William J. Wheeler、Fengjiun Kuo

  DOI：10.1002/jlcr.2580360303

  日期：1995.3

  Two 14 C-isotopomers of duloxetine HCl (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride), a potent mixed serotonin/norepinephrine uptake inhibitor have been prepared by an asymmetric synthesis. The palladium catalyzed cross-coupling of 2-thienoyl chloride (3c) (or its [carbonyl- 14 C] isotopomer 3d) with vinyl tri-n-butyl-stannane, followed by addition of HCl afforded the

  盐酸度洛西汀 (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride) 的两种 14 C-同位素异构体，一种有效的混合血清素/去甲肾上腺素摄取抑制剂已通过不对称方法制备合成。钯催化 2-噻吩酰氯 (3c)（或其 [羰基- 14 C] 同位素异构体 3d）与乙烯基三正丁基锡烷的交叉偶联，然后加入 HCl，得到关键的前手性中间体氯酮（ 5a,b) 在适当的氧氮杂硼烷催化剂（14a 或 b）存在下用硼烷进行手性还原，得到 5-氯代醇（7a）及其 14 C 标记的对应物 7b 或类似的 R-氯代醇（6）。通过与 NaI/丙酮反应活化 7a,b，然后相应的碘醇与甲胺反应产生倒数第二个氨基醇 (8a,b)。与 NaH 形成醇盐，然后与 1-氟萘反应产生度洛西汀或其 14 C-标记的同位素异构体 9。或者，6
• Synthesis of 14C isotopic isomers of tenidap-A novel antiinflammatory agent
  作者：Frank W. Rusek、Fred C. Falkner、Diane L. Johnson、Ralph P. Robinson、Lawrence S. Melvin

  DOI：10.1002/(sici)1099-1344(199603)38:3<207::aid-jlcr841>3.0.co;2-o

  日期：1996.3
• Synthesis of carbon‐14 labelled (3‐{[(Z)‐5‐chloro‐2,3‐dihydro‐3‐(hydroxy‐2‐thienylmethylene)‐2‐oxo‐1 <i>H</i> ‐indol‐1‐yle]carbonylamino}propyl)trimethylammonium chloride, a potential cartilage‐targeted antirheumatic drug
  作者：Isabelle Giraud、Maryse Rapp、Jean‐Michel Dupuy、Jean‐Claude Maurizis、Jean‐Claude Madelmont

  DOI：10.1002/(sici)1099-1344(20000315)43:3<297::aid-jlcr317>3.0.co;2-#

  日期：2000.3.15

  A [C-14]-labelled form of (3-[(Z)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H-indol-1-yle]carbonylamino}propyl)trimethylammonium chloride, a potential cartilage-targeted antirheumatic drug, was required for pharmacokinetic studies. This compound, labelled with [C-14] located in the C-3 methylene position, was prepared in four steps starting from N-[3-(dimethylamino)propyl]-5-chloro-2,3-dihydro-2-oxo-1H-indole-1-carboxamide and 2-thiophene-[C-14]carbonyl chloride, previously synthesized by a two-step sequence from barium [C-14]-carbonate and 2-thienyllithium. The desired product was obtained with a specific activity of 359 MBq/mmol (9.7 mCi/mmol). The overall radiochemical yield was 50% based on barium [C-14]-carbonate.