diethyl 2-((3-hydroxypyridin-2-ylamino)methylene)malonate | 51251-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: diethyl 2-((3-hydroxypyridin-2-ylamino)methylene)malonate
• 英文别名: diethyl N-(3-hydroxypyridinyl-2)aminomethylenemalonate；[(3-hydroxy-pyridin-2-ylamino)-methylene]-malonic acid diethyl ester；Diethyl-<(3-Hydroxy-2-pyridyl)-amino>-methylen-malonat；Diethyl-[(3-Hydroxy-2-pyridyl)-amino]-methylen-malonat；[(3-Hydroxy-2-pyridyl)amino]methylenemalonic Acid, Diethyl Ester；diethyl 2-[[(3-hydroxypyridin-2-yl)amino]methylidene]propanedioate
• CAS: 51251-34-4
• 化学式: C₁₃H₁₆N₂O₅
• 分子量: 280.28
• InChiKey: AYYQWSCWUKMKPI-UHFFFAOYSA-N

物化性质

• 熔点：
  180-181 °C(Solv: acetonitrile (75-05-8))
• 沸点：
  428.1±45.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-((3-hydroxypyridin-2-ylamino)methylene)malonate 以 溶剂黄146 为溶剂， 反应 8.0h， 以78%的产率得到乙基9-羟基-4-氧代-4H-吡啶并[1,2-a]嘧啶-3-羧酸酯
  参考文献：
  名称：

  N，N-二甲基氨基亚甲基丙二酸二乙酯在稠合杂环体系合成中的应用

  摘要：

  研究了N，N-二甲基氨基亚甲基丙二酸二乙酯（3）与N和C-亲核试剂的反应。在3与杂环胺4的反应中，氨基相对于环氮原子在α位连接，在3中的二甲基氨基被杂环氨基取代，得到二乙基杂芳基氨基亚甲基丙二酸酯5，它可以环化成融合的Azino- 6或azolopyrimidinones 7。在反应3带有相对于环氮原子在α位连接的具有活性亚甲基的化合物，例如吡啶基乙腈（8），乙基吡啶基-（9）和喹啉基乙酸酯（10），稠合的喹啉11和12以及苯并[分别形成了c ]喹诺嗪13。在环系统中结合有活性或潜在活性亚甲基的杂环系统，例如吡唑14，嘧啶15和吡啶衍生物18，得到3个稠合的吡喃酮16、17和19，以及二羟基萘22和23萘[ 2,1- b ]吡喃酮24和25。

  DOI：

  10.1002/jhet.5570330407
• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 以27%的产率得到
  参考文献：
  名称：

  YALE H. L., J. HETEROCYCL. CHEM. , 1975, 12, NO 2, 427-431

  摘要：

  DOI：

文献信息

• [EN] 4H-PYRIDO[1,2-a]PYRIMIDIN-4-ONE COMPOUNDS<br/>[FR] COMPOSÉS 4H-PYRIDO [1,2-A] PYRIMIDIN -4-ONE
  申请人：PRANA BIOTECHNOLOGY LTD

  公开号：WO2016086261A1

  公开（公告）日：2016-06-09

  The present invention relates to compounds of the formula I or II: (I) (II) processes for their preparation and their use as pharmaceutical agents or compositions in the treatment, of neurological disorders.

  本发明涉及式I或II的化合物：（I）（II）它们的制备过程以及它们作为药物代理或组合物在治疗神经系统疾病中的应用。
• 9-Substituted-4-oxopyrido(1,2-.alpha.)pyrimidine-3-carboxylic acids and
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US03960847A1

  公开（公告）日：1976-06-01

  9-Substituted-4-oxopyrido[1,2-.alpha.]pyrimidine-3-carboxylic acids and related compounds are disclosed. In addition, their methods of preparation and use as central nervous system depressants and hypotensive agents are taught.

  本发明公开了9-取代-4-氧代吡啶[1,2-α]嘧啶-3-羧酸及其相关化合物。此外，本发明还教授了它们的制备方法以及作为中枢神经系统抑制剂和降压剂的用途。
• Ethene derivatives
  申请人：MAY & BAKER LIMITED

  公开号：EP0174832A2

  公开（公告）日：1986-03-19

  Ethene derivatives of the general formula: wherein R5 represents a heterocyclyl group, containing 1, 2 or 3 rings and one or more heteroatoms selected from nitrogen, oxygen, sulphur and selenium atoms, which is unsubstituted or substituted by one or more substituents R8 [which may be the same or different and each represents a halogen atom or an amino, carboxy, cyano, nitro, hydroxy, oxo, formyl, trifluoromethyl, aryl, aryloxy, arylthio, benzyloxycarbonylamino, sulphamoyl, tetrazol-5-yl, carbamoyl, thiocarbamoyl, arylcarbamoyl or aroyl group, or a straight-or branched-chain alkyl group containing from 1 to 10 carbon atoms, or a straight- or branched-chain alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylamino, alkylsulphamoyl, arylalkyl or arylalkoxy group containing from 1 to 10 carbon atoms in the alkyl moiety, a straight- or branched-chain alkanoyl, alkoxycarbonyl, alkoxycarbonylamino, alkylcarbamoyl or alkanoylamino group containing from 2 to 6 carbon atoms, an N-benzyloxycarbonyl-N-alkylamino group wherein the alkylamino moiety is straight- or branched-chain and contains from 1 to 6 carbon atoms, or a dialkylsulphamoyl, dialkylamino or dialkylcarbamoyl group wherein the alkyl moieties may be straight or branched and may each contain from 1 to 6 carbon atoms and may be linked together to form a ring, or a group of the formula -CR4=CR2R3, or an aryl group which is unsubstituted or substituted by one or more substituents RS (as hereinbefore defined), or a heterocyclylalkyl or arylalkyl group wherein the heterocyclyl or aryl moiety is as hereinbefore defined and the alkyl moiety is straight- or branched-chain and contains 1 or 2 carbons atoms, and R1 represents a group of the general formula: wherein R6 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be substituted by one or more substituents RS (as hereinbefore defined) or an aryl group which may be substituted by one or more substituents R8 (as hereinbefore defined), or R5 represents a quinonoidal group R7 derived from a nitrogen-containing heterocyclyl group within the definition of R5 as hereinbefore defined, bearing on said ring-nitrogen atom a substituent selected from straight- and branched-chain alkyl groups containing from 1 to 6 carbon atoms which may be substituted by one or more substituents RS (as hereinbefore defined), and aryl groups which may be substituted by one or more substituents RS (as hereinbefore defined), and R1 represents an atom =N-, R4 represents a hydrogen atom or a straight- or branched-chain alkoxy or alkylthio group containing from 1 to 6 carbon atoms, a trifluoromethyl group or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be substituted by one or more substituents R8 (as hereinbefore defined), or an aryl group which may be substituted by one or more substituents R8 (as hereinbefore defined), R2 represents a cyano or formyl group, a straight- or branched-chain alkoxycarbonyl or alkylsulphonyl group containing up to 6 carbons, or a dialkylcarbamoyl or dialkylthiocarbamoyl group wherein the alkyl groups may be the same or different and each may be straight or branched and each contains from 1 to 6 carbon atoms, or an aryloxycarbonyl, arylsulphinyl or arylsulphonyl group wherein the aryl moiety may be substituted by one or more substituents R8 (as hereinbefore defined), R3 represents a group within the definition of R2 or a hydrogen atom or a nitro group or an aryl or aroyl group which may be substituted by one or more substituents R8 (as hereinbefore defined) or a straight- or branched-chain alkanoyl group containing up to 6 carbon atoms, and m and n each represents 1 or 2, and pharmaceutically acceptable salts thereof, with the provisos that the following classes of compounds are excluded:- (i) compounds of formula I wherein R5 represents a pyridyl group which is unsubstituted or substituted by one or more substituents R9 which may be the same or different and each represents a group within the definition of Re other than oxo, straight- or branched-chain alkyl containing from 7 to 10 carbon atoms, straight- or branched-chain alkoxy, alkylthio, alkylsulphonyl, alkylamino, alkylsulphamoyl or arylalkyl containing from 7 to 10 carbon atoms in the alkyl moiety, straight- or branched-chain alkylsulphinyl or arylalkoxy containing from 1 to 10 carbon atoms in the alkyl moiety, or a group -CR4=CR2R3 as hereinbefore defined, R2 and R3 may be the same or different and each represents a phenylsulphonyl group which may be unsubstituted or substituted by one or more substituents R9 (as hereinbefore defined), R' represents a group of formula II, R4 and R6 represent hydrogen atoms and m and n both represent 1; (ii) compounds of formula I wherein R5 represents a 5-halogenopyrid-2-yl group, R2 and R3 both represent cyano groups, R1 represents a group of formula II, R4 and R° represent hydrogen atoms and m and n both represent 1; and (iii) compounds of formula I wherein R5 represents a 1,2,4-triazolo[4,8-a]-quinoline group which is unsubstituted or substituted by one or more substituents R10 which may be the same or different and each represents a group within the definition of R9 or a straight- or branched-chain alkylsulphinyl group containing from 1 to 6 carbon atoms, R2 and R3 may be the same or different and each represents a cyano group, a straight- or branched-chain alkoxycarbonyl group containing from 2 to 6 carbon atoms, or a phenylsulphonyl group which may be unsubstituted or substituted by one or more substituents R10 (as hereinbefore defined), R' represents a group of formula II, R4 and R6 represent hydrogen atoms and m and n both represent 1, possess useful pharmacological properties.

  以下是对文本的中文翻译： **丙烯衍生物的通式**： 其中，R5代表一个杂环基，包含1、2或3个环，并且含有1个或多个选自氮、氧、硫和硒原子的杂原子，该杂环基可以是未取代的，或被一个或多个R8取代基取代（R8可以相同或不同，每个R8代表一个卤素原子；或者一个氨基、羧基、氰基、硝基、羟基、羰基、甲酰基、三氟甲基、芳基、芳氧基、芳硫基、苄氧羰基氨基、硫脲基、5-四唑基、羰基氨基、硫代羰基氨基、芳基羰基氨基或芳酰基；或者一个直链或支链烷基，含有1至10个碳原子；或者一个直链或支链烷氧基、烷硫基、烷亚砜基、烷砜基、烷氨基、烷硫脲基、芳基烷基或芳基烷氧基，其中烷基部分含有1至10个碳原子；或者一个直链或支链烷酰基、烷氧基羰基、烷氧基羰基氨基、烷基羰基氨基或烷酰基氨基，含有2至6个碳原子；或者一个N-苄氧羰基-N-烷基氨基，其中烷基氨基部分为直链或支链，含有1至6个碳原子；或者一个二烷基硫脲基、二烷基氨基或二烷基羰基氨基，其中烷基部分可以为直链或支链，每个烷基部分含有1至6个碳原子，且烷基部分可以彼此连接形成一个环；或者一个通式为-CR4=CR2R3的基团；或者一个未取代的芳基，或被一个或多个R8取代基取代的芳基；或者一个杂环基烷基或芳基烷基，其中杂环基或芳基部分如前所定义，烷基部分为直链或支链，含有1或2个碳原子）。 R1代表一个通式为的基团： 其中，R6代表一个氢原子；或一个直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 此外，R5还可以代表一个由含氮杂环基衍生而来的醌状基团R7，该杂环基如前所定义的R5，其中环氮原子上取代有一个选自以下的基团：直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 R1代表一个=NH原子；R4代表一个氢原子，或一个直链或支链烷氧基、烷硫基，含有1至6个碳原子；或一个三氟甲基基团；或一个直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 R2代表一个氰基或甲酰基；或一个直链或支链烷氧基羰基或烷硫基，含有不超过6个碳原子；或一个二烷基羰基氨基或二烷基硫代羰基氨基，其中两个烷基可以相同或不同，每个烷基为直链或支链，含有1至6个碳原子；或一个芳氧基羰基、芳硫基或芳硫基羰基，其中芳基部分可以被一个或多个R8取代基取代（如前所定义）。 R3代表一个与R2定义范围内的基团，或一个氢原子；或一个硝基；或一个芳基；或一个芳酰基，可以被一个或多个R8取代基取代（如前所定义）；或一个直链或支链烷酰基，含有不超过6个碳原子。 m和n各自代表1或2。 除以下化合物类别外，上述结构及其药学上可接受的盐类具有有用的药理学性质： (i) 通式为I的化合物，其中R5代表一个吡啶基，该吡啶基可以是未取代的，或被一个或多个R9取代基取代，R9可以相同或不同，每个R9代表一个基团，其定义范围包括：R8（但不包括氧代基、直链或支链烷基，含有7至10个碳原子；直链或支链烷氧基、烷硫基、烷硫基、烷氨基、烷硫脲基、或芳基烷基，其中烷基部分含有7至10个碳原子；直链或支链烷亚砜基，或芳基烷氧基，其中烷基部分含有1至10个碳原子）；或一个如前所定义的-CR4=CR2R3基团。其中，R2和R3可以相同或不同，各自代表一个苯硫基，可以是未取代的，或被一个或多个R9取代基取代（如前所定义）。R’代表一个通式II的基团。R4和R6代表氢原子，m和n均为1。 (ii) 通式为I的化合物，其中R5代表一个5-卤素取代吡啶-2-基，R2和R3均为氰基，R1代表一个通式II的基团，R4和R°代表氢原子，m和n均为1。 (iii) 通式为I的化合物，其中R5代表一个1,2,4-三唑[4,8-a]-喹啉基，该基团可以是未取代的，或被一个或多个R10取代基取代，R10可以相同或不同，每个R10代表一个基团，其定义范围包括：R9（如前所定义），或一个直链或支链烷亚砜基，含有1至6个碳原子。R2和R3可以相同或不同，各自代表一个氰基、一个直链或支链烷氧基羰基（含有2至6个碳原子），或一个苯硫基，可以是未取代的，或被一个或多个R10取代基取代（如前所定义）。R’代表一个通式II的基团。R4和R6代表氢原子，m和n均为1。 上述化合物在排除了特定结构后，具有有用的药理学性质。
• 4H-pyrido[1,2-A]pyrimidin-4-one compounds
  申请人：Prana Biotechnology Limited

  公开号：US10287285B2

  公开（公告）日：2019-05-14

  The present invention relates to compounds of the formula I or II: (I) (II) processes for their preparation and their use as pharmaceutical agents or compositions in the treatment, of neurological disorders.

  本发明涉及式 I 或式 II 的化合物：(I) (II) 它们的制备工艺及其作为药剂或组合物治疗神经系统疾病的用途。
• 4H-pyrido[1,2-a]pyrimidin-4-one compounds
  申请人：Prana Biotechnology Limited

  公开号：US11008319B2

  公开（公告）日：2021-05-18

  The present invention relates to compounds of the formula I or II: (I) (II) processes for their preparation and their use as pharmaceutical agents or compositions in the treatment, of neurological disorders.

  本发明涉及式 I 或式 II 的化合物：(I) (II) 它们的制备工艺及其作为药剂或组合物治疗神经系统疾病的用途。