ethyl 2-formyl-3-(2-methoxy-pyridin-4-yl)propionate | 72716-88-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-formyl-3-(2-methoxy-pyridin-4-yl)propionate
• 英文别名: ethyl 2-formyl-3-(2-methoxy-4-pyridyl)-propionate；ethyl 2-formyl-3-(2-methoxy-4-pyridyl)propionate；ethyl 2-formyl-3-(2-methoxypyridin-4-yl)propanoate
• CAS: 72716-88-2
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: IYKMWZAVCXVYJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  339.9±42.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-formyl-3-(2-methoxy-pyridin-4-yl)propionate 在 吡啶 、 氨 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 42.0h， 生成 2-Amino-5-(2-methoxy-pyridin-4-ylmethyl)-1H-pyrimidin-4-one
  参考文献：
  名称：

  Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK&F 93574) and related compounds

  摘要：

  The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described. Side-chains associated with H-2-antagonist activity am attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring. Good H-2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H-2-receptor. High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models led to compound 16c, 2-[2-(5-dimethylaminomethyl-2-furanylmethyl-thio)ethylamino]-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK&F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.

  DOI：

  10.1016/0223-5234(93)90091-r
• 作为产物：
  描述：

  4-氰基-2-甲氧基吡啶 在 palladium on activated charcoal 、 镍 哌啶 、 吡啶 、 盐酸 、 聚合甲醛 、 氢气 、 盐酸氨基脲 、 sodium acetate 、 sodium hydride 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 20.5h， 生成 ethyl 2-formyl-3-(2-methoxy-pyridin-4-yl)propionate
  参考文献：
  名称：

  Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK&F 93574) and related compounds

  摘要：

  The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described. Side-chains associated with H-2-antagonist activity am attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring. Good H-2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H-2-receptor. High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models led to compound 16c, 2-[2-(5-dimethylaminomethyl-2-furanylmethyl-thio)ethylamino]-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK&F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.

  DOI：

  10.1016/0223-5234(93)90091-r

文献信息

• Intermediates in the process for making histamine antagonists
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04227000A1

  公开（公告）日：1980-10-07

  A process for making substituted 2-aminopyrimidones which are histamine H.sub.2 - antagonists which comprises reacting a 2-nitroaminopyrimidone with a heteroarylalkylamine, heteroarylalkylthioalkylamine, or heteroarylalkoxyalkylamine. One particular compound which can be made by this process is 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-5-[5-(1,3-benzodioxolyl) methyl]-4-pyrimidone. Also claimed are 2-nitroaminopyrimidone intermediates for use in this process. One specific intermediate is 2-nitroamino-5-[5-(1,3-benzodioxolyl)methyl]-4-pyrimidone.

  一种制备取代2-氨基嘧啶酮的方法，这些化合物是组胺H.sub.2-拮抗剂，包括将2-硝基氨基嘧啶酮与杂环烷基胺、杂环烷基硫代烷基胺或杂环烷基氧代烷基胺反应。通过这种方法可以制备一种特定化合物，即2-[2-(5-甲基-4-咪唑基甲硫基)乙基氨基]-5-[5-(1,3-苯并二氧杂环己基)甲基]-4-嘧啶酮。此外，还声明了用于该方法的2-硝基氨基嘧啶酮中间体。其中一个特定的中间体是2-硝基氨基-5-[5-(1,3-苯并二氧杂环己基)甲基]-4-嘧啶酮。
• Pyrimidine compounds
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04649141A1

  公开（公告）日：1987-03-10

  The compounds are substituted pyrimidine compounds which are histamine H.sub.2 -antagonists. A specific compound of the present invention is 2-[2-(5-dimethylaminomethyl)-2-furylmethylthio)ethylamino]-5-(3-pyridylmet hyl)-4-pyrimidone.

  这些化合物是取代嘧啶化合物，是组胺H.sub.2 -拮抗剂。本发明的一种特定化合物是2-[2-(5-二甲氨基甲基)-2-呋喃甲硫基)乙基氨基]-5-(3-吡啶甲基)-4-嘧啶酮。
• Process and nitroaminopyrimidone intermediates for histamine H.sub.2
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04523015A1

  公开（公告）日：1985-06-11

  A process for making substituted 2-aminopyrimidones which are histamine H.sub.2 -antagonists which comprises reacting a 2-nitroaminopyrimidone with a heteroarylalkylamine, heteroarylalkylthioalkylamine, or heteroarylalkoxyalkylamine. One particular compound which can be made by this process is 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-5-[5-(1,3-benzodioxyolyl )methyl]-4-pyrimidone. Also claimed are 2-nitroaminopyrimidone intermediates for use in this process. One specific intermediate is 2-nitroamino-5-[5-(1,3-benzodioxyolyl)methyl]-4-pyrimidone.

  一种制备取代的2-氨基嘧啶酮的方法，这些化合物是组胺H.sub.2-拮抗剂，包括将2-硝基氨基嘧啶酮与杂环烷基胺，杂环烷基硫代烷基胺或杂环烷基氧代烷基胺反应。该方法可以制备出一种特定的化合物，即2-[2-(5-甲基-4-咪唑基甲硫基)乙基氨基]-5-[5-(1,3-苯并二氧杂环基)甲基]-4-嘧啶酮。还声明了用于该方法的2-硝基氨基嘧啶酮中间体。其中一个具体的中间体是2-硝基氨基-5-[5-(1,3-苯并二氧杂环基)甲基]-4-嘧啶酮。
• Pyrimidone derivatives
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0087274A2

  公开（公告）日：1983-08-31

  The invention provides histamine H2-antaponist compounds of formula (1):- and pharmaceutically acceptable salts thereof, where W is a 2-furanyl or 2-thienyl group optionally substituted in the 5-position with a group R1R2N(CH2)a-; a 2-pyridyl group optionally substituted in the 4- or 6-position with a group R1R2N(CH2)a-; a phenyl group substituted in the 3-or 4-position with a group R1R2N(CH2)a-; a 4-imidazolyl group optionally substituted in the 5-position with methyl or bromine; a 2-pyridyl group optionally substituted in the 3-position with C1-4 alkyl, C1-4, alkoxy, halogen, amino or hydroxy; a 2-thiazolyl group or a 2-guanidino-4-thiazolyl group; X is (CH2)b in which b is from 3 to 6, or (CH2)dS(CH2)e in which dand e are the same or different and are from 1 to 3 or, when W is substituted phenyl or 2-pyridyl substituted in the 4- or 6- position with a group R1R2N(CH2)a-, O(CH2)t in which f is from 2 to 5; Z is hydrogen or C1-4 alkyl; A is C1-C5 alkylene or (CH2)pA1(CH2)q- where A' is oxygen or sulphur and p and q are such that their sum is from 1 to 4; B is an optionally substituted pyridyl, where the optional substituent is one or more C1-4 alkyl, or C1-4 alkoxy or hydroxy groups or halogen atoms or an N-oxo group or a phenyl group optionally substituted with one or more C1-4 alkyl or C1-4 alkoxy groups or halogen atoms or B is a 6-(2,3-dihydro-1,4-benzodioxinyl) or a 5-(1,3-benzodioxolyl) group or B is a 2-furanyl or 2-thienyl group optionally substituted in the 5-position with a group R1R2N(CH2)a-; a phenyl group substituted in the 3- of 4-position with a group R1R2N(CH2)a- or a 3-pyridyl group substituted in the 5- or 6-position or a 4-pyridyl group substituted in the 2-position by a group R1R2N(CH2)a-; R' and R2 can be the same or different and are hydrogen or C1-4 alkyl or together form a 1,4-butanediyl, 1,5-pentanediyl, 1,6-hexanediyl or 1,7-heptanediyl group; and a is 1 to 4.

  本发明提供了式(1)的组胺 H2- 拮抗剂化合物 及其药学上可接受的盐类，其中 W 是在 5 位上任选被基团 R1R2N(CH2)a- 取代的 2-呋喃基或 2-噻吩基； 在 4 或 6 位上任选被基团 R1R2N( )a- 取代的 2-吡啶基； 在 3 或 4 位上任选被基团 R1R2N( )a- 取代的苯基；在 5 位上任选被甲基或溴取代的 4-咪唑基； 在 3 位上任选被 C1-4 烷基、C1-4、烷氧基、卤素、氨基或羟基取代的 2-吡啶基； 2-噻唑基或 2-胍基-4-噻唑基； X为( )b，其中 b 为 3 至 6，或( )dS( )e，其中 d 和 e 相同或不同且为 1 至 3，或当 W 为在 4 或 6-位被基团 R1R2N( )a- 取代的取代苯基或 2-吡啶基时，为 O( )t，其中 f 为 2 至 5； Z 是氢或 C1-4 烷基； A 是 C1-C5 亚烷基或 ( )pA1( )q- 其中 A' 是氧或硫，p 和 q 之和为 1 至 4； B 是任选取代的吡啶基，其中任选取代基是一个或多个 C1-4 烷基或 C1-4 烷氧基或羟基或卤素原子或 N-氧代基团或任选被一个或多个 C1-4 烷基或 C1-4 烷氧基或卤素原子取代的苯基或 B 是 6-(2、或 B 是 6-(2,3-二氢-1,4-苯并二恶茂基)或 5-(1,3-苯并二恶茂基)基团，或 B 是 2-呋喃基或 2-噻吩基基团，可选择在 5 位被 R1R2N( )a-基团取代；在 3 位或 4 位被基团 R1R2N( )a- 取代的苯基，或在 5 位或 6 位被基团 R1R2N( )a- 取代的 3-吡啶基，或在 2 位被基团 R1R2N( )a- 取代的 4-吡啶基； R'和 R2 可以相同或不同，并且是氢或 C1-4 烷基，或共同形成 1,4-丁二基、1,5-戊二基、1,6-己二基或 1,7-庚二基；且 a 为 1 至 4。
• Chemical process for preparing H2-antagonists
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0112637A2

  公开（公告）日：1984-07-04

  A chemical process is described for the preparation of H2-antagonists or precursors thereof, of the formula (V): wherein R' is 5-methylimidazol-4-yl, furan-2-yl or 5-dimeth- ylaminomethylfuran-2-yl and R2 is 3,4-methylenedioxyphenyl or optionally protected 2-hydroxypyrid-4-yl; which process comprises reacting a compound of the formula (VI) with a compound of the formula (VII): wherein R3 is C1-6alkyl; and thereafter if desired deprotecting a protected hydroxy group, converting a compound wherein R1 is furan-2-yl into a compound wherein R1 is 5-di- methylaminomethylfuran-2-yl, and/or forming a pharmaceutically acceptable salt.

  描述了一种制备式(V)的 H2-拮抗剂或其前体的化学工艺： 其中 R'为 5-甲基咪唑-4-基、呋喃-2-基或 5-二甲基氨基甲基呋喃-2-基，R2 为 3,4-亚甲基二氧苯基或经选择保护的 2-羟基吡啶-4-基；该工艺包括使式（VI）化合物与式（VII）化合物反应： 其中 R3 为 C1-6 烷基；然后，如果需要，对受保护的羟基进行脱保护，将 R1 为呋喃-2-基的化合物转化为 R1 为 5-二甲氨基甲基呋喃-2-基的化合物，和/或形成药学上可接受的盐。