(3aS,6aR)-1-[(R)-1-phenylethyl]-3-benzyltetrahydro-1H-thieno[3,4-d]imidazol-2,4-dione

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3aS,6aR)-1-[(R)-1-phenylethyl]-3-benzyltetrahydro-1H-thieno[3,4-d]imidazol-2,4-dione
• 英文别名: (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]-imidazol-2,4(3H,3aH)-dione；(3aR,6aS)-1-benzyl-3-[(1R)-1-phenylethyl]-4,6a-dihydro-3aH-thieno[3,4-d]imidazole-2,6-dione
• 化学式: C₂₀H₂₀N₂O₂S
• 分子量: 352.457
• InChiKey: NURXGLFUPWTIHX-JLSDUUJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3aS,6aR)-1-[(R)-1-phenylethyl]-3-benzyltetrahydro-1H-thieno[3,4-d]imidazol-2,4-dione 在 硫酸 、 magnesium 、 1,2-二溴乙烷 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 17.5h， 生成
  参考文献：
  名称：

  Process Development Implications of Biotin Production Scale-Up

  摘要：

  Careful planning and construction of suitable in-process tests and isolation of new impurities observed led to quick, mechanistic-based assessments of problems seen in two steps of Biotin production scale-up and allowed for rapid changes to be made to resolve the issues. The quench of Grignard reaction mixtures with deuterium-based materials led to increased understanding of one of the main pathways for yield loss in a Grignard reaction contained with the Biotin process.

  DOI：

  10.1021/op020089o
• 作为产物：
  描述：

  (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-furo[3,4-d]imidazol-2,4(3H,3aH)-dione 、 potassium thioacetate 生成 (3aS,6aR)-1-[(R)-1-phenylethyl]-3-benzyltetrahydro-1H-thieno[3,4-d]imidazol-2,4-dione
  参考文献：
  名称：

  MCGARRITY, JOHN;TENUD, LEANDER

  摘要：

  DOI：

文献信息

• Process for the production of (+) biotin
  申请人：Lonza Ltd.

  公开号：US05162540A1

  公开（公告）日：1992-11-10

  (3aS,6aR)-[(R)-(1-phenylethyl)-3,4-methoxybenzyl dihydro-1H-furo-[3,4-d]-imidazol-2,4(3H,3aH)-dione and 1H-furo-[3,4-d]-imidazol-2,4-(3H,3aH)-dione derivatives which are useful as intermediates for preparing (+) biotin, also known as vitamin H.

  （3aS，6aR）-[(R)-(1-苯乙基)-3,4-甲氧基苯甲基]二氢-1H-呋喃-[3,4-d]-咪唑-2,4（3H,3aH）-二酮和1H-呋喃-[3,4-d]-咪唑-2,4（3H,3aH）-二酮衍生物可作为制备（+）生物素，也称为维生素H的中间体。
• Process for the production of biotin precursors
  申请人：Lonza Ltd.

  公开号：US04851540A1

  公开（公告）日：1989-07-25

  Process for the production of imidazole derivatives of the formula: ##STR1## wherein R.sub.1 is an (R)- or (S)-1-phenylalkyl group, an (R)- or (S)-1-alkoxycarbonyl-1-phenylmethyl group or an (R)- or (S)-1-aryloxycarbonyl-1-phenylmethyl group, R.sub.2 is hydrogen, a substituted or unsubstituted alkanoyl group, an unsubstituted or a substituted benzoyl group, a substituted or an unsubstituted benzyl group, an alkoxycarbonyl group, and aryloxycarbonyl group, an alkoxyalkyl group, a pyranyl group, a substituted or unsubstituted benzenesulfonyl group, an alkylsulfonyl group, a diarylphosphinyl group, a dialkoxyphosphinyl group or a trialkylsilyl group, and A is a sulfur or oxygen atom. A tetronic acid of the formula: ##STR2## wherein A has the above-mentioned meaning, is reacted with a diazonium salt, converting the resultant arylazotetronic acid or the tautomeric arylhydrazone in a further step with a chiral amine into an arylazoamino compound, reducing the arylazoamino compound, converting the resultant diamine, with phosgene or a phosgene-equivalent reagent, into the corresponding imidazole and optionally introducing a protective group by reaction with a substituted or unsubstituted aliphatic or aromatic acid chloride, an aliphatic or aromatic carboxylic acid anhydride, a haloformic acid alkyl ester, a 1-alkoxyalkyl halide, an enol ether, an aromatic or aliphatic sulfonic acid halide, a diarylphosphinic acid halide, a phosphoric acid dialkyl ester halide, a trialkyl silyl halide or a trialkyl silyl acetamide. These imidazole derivatives are suitable as intermediate products for the production of (+) biotin.

  制备式为：##STR1## 其中R.sub.1是(R)-或(S)-1-苯基烷基，(R)-或(S)-1-烷氧羰基-1-苯甲基，或(R)-或(S)-1-芳基氧羰基-1-苯甲基，R.sub.2是氢、取代或未取代的烷酰基、取代或未取代的苯甲酰基、取代或未取代的苯甲基、烷氧羰基、芳基氧羰基、烷氧基烷基、吡喃基、取代或未取代的苯磺酰基、烷基磺酰基、二芳基膦基、二烷氧基膦基或三烷基硅基，A是硫或氧原子的咪唑衍生物的制备方法。式中的A具有上述含义，反应一种式为：##STR2## 其中A具有上述含义，与重氮盐反应，将所得的芳基偶氮酮酸或互变异构体芳基腙在进一步步骤中与手性胺反应成芳基偶氮氨基化合物，还原芳基偶氮氨基化合物，将所得的二胺与光气或光气等效试剂反应成相应的咪唑，并通过与取代或未取代的脂肪族或芳香族酸氯化物、脂肪族或芳香族羧酸酐、卤代甲酸烷基酯、1-烷氧基烷基卤化物、烯醇醚、芳香族或脂肪族磺酸卤化物、二芳基膦酸卤化物、磷酸二烷基酯卤化物、三烷基硅基卤化物或三烷基硅基乙酰胺反应引入保护基。这些咪唑衍生物适用于生产(+)生物素的中间产品。
• Chiral biotin precursors
  申请人：Lonza Ltd.

  公开号：US04873339A1

  公开（公告）日：1989-10-10

  Imidazole derivatives of the formula: ##STR1## wherein R.sub.1 is an (R)- or (S)-1-phenylalkyl group, an (R)- or (S)-1-alkoxycarbonyl-1-phenylmethyl group or an (R)- or (S)-1-aryloxycarbonyl-1-phenylmethyl group, R.sub.2 is hydrogen, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted benzoyl group, a substituted or unsubstituted benzyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkoxyalkyl group, a pyranyl group, a substituted or unsubstituted benzenesulfonyl group, an alkylsufonyl group, a diarylphosphinyl group, a dialkoxyphosphinyl group or a trialkylsilyl group, and A is a sulfur or oxygen atom. The imidazole derivatives are intermediate products for the production of (+) biotin.

  配方为：##STR1## 的咪唑衍生物，其中R.sub.1是(R)-或(S)-1-苯基烷基，(R)-或(S)-1-烷氧羰基-1-苯甲基，或(R)-或(S)-1-芳氧羰基-1-苯甲基。R.sub.2是氢，取代或未取代的烷酰基，取代或未取代的苯甲酰基，取代或未取代的苯甲基，烷氧羰基，芳氧羰基，烷氧基烷基，吡喃基，取代或未取代的苯磺酰基，烷基磺酰基，二芳基膦基，二烷氧基膦基或三烷基硅基，而A是硫或氧原子。咪唑衍生物是生产(+)生物素的中间产物。
• Verfahren zur Herstellung von (+)-Biotin
  申请人：LONZA AG

  公开号：EP0273270A1

  公开（公告）日：1988-07-06

  Die Erfindung betrifft ein neues Verfahren zur Herstellung von (+)-Biotin.

  本发明涉及一种生产(+)-生物素的新工艺。
• Verfahren zur Herstellung von 1,3-substituiertem Tetrahydro-1H-thieno-[3,4-d]-imidazol-2(3H)-on-4-yliden-pentansäureester
  申请人：LONZA AG

  公开号：EP0387747A1

  公开（公告）日：1990-09-19

  1,3-substituierte Tetrahydro-1H-thieno-[3,4-d]-imidazol-­2(3H)-on-4-yliden-pentansäureester sind wichtige Zwischen­produkte für die Herstellung der pharmazeutischen Wirksub­stanz (+)-Biotin. Es wird ein verbessertes Verfahren zur Herstellung dieser Zwischenstufe vorgeschlagen.

  1,3-取代的四氢-1H-噻吩-[3,4-d]-咪唑-2(3H)-酮-4-亚基戊酸酯是生产活性药物成分 (+)- 生物素的重要中间体。 本文提出了一种生产这种中间体的改进工艺。