2-氯-3-(1-羟基-4-甲氧基苯基甲基)吡嗪 | 121246-87-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-氯-3-(1-羟基-4-甲氧基苯基甲基)吡嗪
• 英文名称: 2-chloro-3-(1-hydroxy-4-methoxyphenylmethyl)pyrazine
• 英文别名: (2-chloropyrazin-3-yl)(4-methoxyphenyl)methanol；2-Chloropyrazin-3-yl 4-methoxyphenyl methanol；(3-chloropyrazin-2-yl)-(4-methoxyphenyl)methanol
• CAS: 121246-87-5
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: GQGYVHZXUJQVRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-3-(1-羟基-4-甲氧基苯基甲基)吡嗪 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 碘 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.25h， 以64%的产率得到2-chloro-3-(1-hydroxy-4-methoxyphenylmethyl)-6-iodopyrazine
  参考文献：
  名称：

  通过吡嗪的受控金属化而生成Septorin的新路线。恶魔XXX

  摘要：

  已经研究了在四氢呋喃中用LTMP对2-氯-3-（1-羟基-4-烷氧基苯基甲基）吡嗪进行金属化，并在C 6上提供了区域选择性官能化的化合物。这种区域选择性是通过应用梯度增强的HMBC序列建立的，以观察自然丰度下的长距离1 H- 15 N异核偶联以及X射线衍射。与在C 6的区域选择性金属化相关，过渡金属催化的交叉偶联反应提供了通往Septorin的新途径。

  DOI：

  10.1016/s0040-4020(01)00950-4
• 作为产物：
  描述：

  2-氯吡嗪 、 4-甲氧基苯甲醛 在 2,2,6,6-四甲基哌啶 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以89%的产率得到2-氯-3-(1-羟基-4-甲氧基苯基甲基)吡嗪
  参考文献：
  名称：

  通过吡嗪的受控金属化而生成Septorin的新路线。恶魔XXX

  摘要：

  已经研究了在四氢呋喃中用LTMP对2-氯-3-（1-羟基-4-烷氧基苯基甲基）吡嗪进行金属化，并在C 6上提供了区域选择性官能化的化合物。这种区域选择性是通过应用梯度增强的HMBC序列建立的，以观察自然丰度下的长距离1 H- 15 N异核偶联以及X射线衍射。与在C 6的区域选择性金属化相关，过渡金属催化的交叉偶联反应提供了通往Septorin的新途径。

  DOI：

  10.1016/s0040-4020(01)00950-4

文献信息

• A New Route to 2,3-Disubstituted Pyrazines; Regioselective Metalation of Chloropyrazine
  作者：A. Turck、L. Mojovic、G. Quéguiner

  DOI：10.1055/s-1988-27736

  日期：——

  Chloropyrazine is regioselectively metalated by lithium amides in tetrahydrofuran to give 3-chloro-2-lithiopyrazine. The reaction of this lithio derivative with electrophiles can either be performed in situ (with the electrophile, e. g., chlorotrimethylsilane, present in the mixture already during metalation), i. e., by the "equilibrium shift" procedure, or with the solution of the preformed lithio derivative, i. e., by the "accumulation" procedure. With aldehydes and benzophenone, the "accumulation" procedure affords 3-chloro-2-(1-hydroxyalkyl)pyrazines in good yields. The secondary alcohols thus obtained can be oxidized to 2-acyl-3-chloropyrazines with manganese(IV) oxide and these ketones can be converted into 3-acyl-2-aminopyrazines by reaction with ammonia in ethanol; cyclization of 3-chloro-2-(2-methoxybenzoyl) pyrazine using pyridine hydrochloride at 210°C affords 10-oxo-10H-[1] benzopyrano[2,3-b]pyrazine (1,4-diazaxanthone) in high yield. 3-Chloro-2-formylpyrazine is obtained by reaction of the lithio derivative with ethyl formate and 3-chloropyrazine-2-carboxylic acid by reaction with carbon dioxide.

  氯吡嗪在四氢呋喃中被锂胺区域选择性地金属化，生成3-氯-2-锂吡嗪。该锂衍生物与电亲体的反应可以通过“平衡移位”程序在原位进行（电亲体，如氯三甲基硅烷，在金属化过程中已存在于混合物中），也可以通过“积累”程序与预先形成的锂衍生物的溶液进行。在醛类和二苯甲酮的反应中，“积累”程序可以高产量地得到3-氯-2-(1-羟基烷基)吡嗪。由此获得的二级醇可以通过四氧化锰氧化为2-酰基-3-氯吡嗪，而这些酮可以通过与氨在乙醇中的反应转化为3-酰基-2-氨基吡嗪；在210°C下使用盐酸吡啶对3-氯-2-(2-甲氧基苯甲酰)吡嗪进行环化，可以高产量地得到10-氧代-10H-[1]苯并吡喆烷[2,3-b]吡嗪（1,4-二氮杂喹啉）。3-氯-2-甲酰吡嗪通过锂衍生物与乙酸乙酯的反应以及3-氯吡嗪-2-羧酸与二氧化碳的反应获得。
• Nitrogenous heterocyclic derivative, medicinal composition containing the same, medical use thereof, and intermediate therefor
  申请人：Nishimura Toshihiro

  公开号：US20050049203A1

  公开（公告）日：2005-03-03

  The present invention provides nitrogen-containing heterocyclic derivatives represented by the general formula: wherein X 1 and X 3 independently represent N or CH; X 2 represents N or CR 2 ; X 4 represents N or CR 3 ; and with the proviso that one or two of X 1 , X 2 , X 3 and X 4 represent N; R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted(lower alkoxy) group, a lower alkoxy(lower alkoxy) -substituted (lower alkyl) group, a cyclic lower alkyl group, a halo(lower alkyl) group or a group represented by the general formula: HO-A—wherein A represents a lower alkylene group, a lower alkyleneoxy group or a lower alkylenethio group; R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group, a cyclic lower alkyl group, a lower alkoxy group, an amino group, a (lower acyl)amino group, a mono(lower alkyl)amino group or a di(lower alkyl)amino group; and R 3 represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, or prodrugs thereof which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses and production intermediates thereof.

  本发明提供了一种以通式表示的含氮杂环衍生物： 其中，X1和X3独立地表示N或CH；X2表示N或CR2；X4表示N或CR3；并且假定X1、X2、X3和X4中的一个或两个表示N；R1表示氢原子、卤素原子、低碳基、低烷氧基、低硫代烷基、低烷氧基取代的（低烷基）基团、低烷氧基取代的（低烷氧基）基团、低烷氧基（低烷氧基）取代的（低烷基）基团、环状低烷基、卤素（低烷基）基团或由通式HO-A-表示的基团，其中A表示低碳亚烷基、低碳亚烷氧基或低碳亚烷硫基；R2表示氢原子、卤素原子、低碳基、环状低碳基、低烷氧基、氨基、（低酰基）氨基、单（低烷基）氨基或双（低烷基）氨基；R3表示氢原子或低碳基，或其药学上可接受的盐，或其前药，其作为预防或治疗与高血糖相关的疾病，如糖尿病、糖尿病并发症或肥胖症的药剂，包括这些药剂的制剂和制备中间体。
• Nitrogenous heterocyclic derivatives, medicinal compositions containing the same, medicinal uses thereof, and intermediates therefor
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：US07271153B2

  公开（公告）日：2007-09-18

  The present invention provides nitrogen-containing heterocyclic derivatives represented by the general formula: wherein X1 and X3 independently represent N or CH; X2 represents N or CR2; X4 represents N or CR3; and with the proviso that one or two of X1, X2, X3 and X4 represent N; R1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group, a lower alkoxy(lower alkoxy)-substituted (lower alkyl) group, a cyclic lower alkyl group, a halo(lower alkyl) group or a group represented by the general formula: HO-A- wherein A represents a lower alkylene group, a lower alkyleneoxy group or a lower alkylenethio group; R2 represents a hydrogen atom, a halogen atom, a lower alkyl group, a cyclic lower alkyl group, a lower alkoxy group, an amino group, a (lower acyl)amino group, a mono(lower alkyl)amino group or a di(lower alkyl)amino group; and R3 represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, or prodrugs thereof which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses and production intermediates thereof.

  本发明提供了一种由通式表示的含氮杂环衍生物： 其中X1和X3分别独立地表示N或CH；X2表示N或CR2；X4表示N或CR3；并且在X1、X2、X3和X4中的一个或两个表示N；R1表示氢原子、卤原子、低碳基、低烷氧基、低烷硫基、低烷氧基取代的（低碳基）基团、低烷氧基取代的（低烷氧基）基团、低烷氧基（低烷氧基）取代的（低碳基）基团、环状低碳基、卤（低碳基）基团或由通式HO-A-表示的基团，其中A表示低碳亚基、低碳亚氧基或低碳硫基；R2表示氢原子、卤原子、低碳基、环状低碳基、低烷氧基、氨基、（低酰基）氨基、单（低碳基）氨基或双（低碳基）氨基；R3表示氢原子或低碳基，或其药学上可接受的盐，或其前药，其用作预防或治疗与高血糖相关的疾病，如糖尿病、糖尿病并发症或肥胖症的药剂，以及包含它们的制药组合物和制药用途和中间体。
• NITROGENOUS HETEROCYCLIC DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF AND INTERMEDIATE THEREFOR
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1405859A1

  公开（公告）日：2004-04-07

  The present invention is to provide a nitrogen-containing heterocyclic derivative represented by the general formula (I) or a pharmaceutically acceptable salt thereof, or a prodrug thereof, which exerts an excellent inhibitory activity in human SGLT2 and is useful as an agent for the prevention or treatment of a disease associated with hyperglycemia such as diabetes etc., or a pharmaceutical composition comprising the same and a pharmaceutical use thereof and a production intermediate thereof. In the general formula (I), X1 and X3 are N or CH; X2 is N or CR2; X4 is N or CR3; and with the proviso that one or two of X1, X2, X3 and X4 are N; and R1, R2 and R3 are a hydrogen atom etc.

  本发明旨在提供一种由通式(I)代表的含氮杂环衍生物或其药学上可接受的盐，或其原药，该衍生物对人SGLT2具有优异的抑制活性，可作为预防或治疗糖尿病等与高血糖相关疾病的药物，或由其组成的药物组合物及其药物用途和其生产中间体。在通式（I）中，X1 和 X3 是 N 或 CH；X2 是 N 或 CR2；X4 是 N 或 CR3；但条件是 X1、X2、X3 和 X4 中的一个或两个是 N；R1、R2 和 R3 是氢原子等。
• EP1405859
  申请人：——

  公开号：——

  公开（公告）日：——

表征谱图