1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ²-pyrrolin-5-one | 66666-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ²-pyrrolin-5-one
• 英文别名: 1-(2-Methyl-4-aminopyrimidin-5-yl)-methyl-2-methyl-3-(2-hydroxyethyl)-4-hydroxy-4-(2-methoxyphenyl)-Δ²-pyrrolin-5-on；1-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-3-hydroxy-4-(2-hydroxy-ethyl)-3-(2-methoxy-phenyl)-5-methyl-1,3-dihydro-pyrrol-2-one；1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-hydroxy-4-(2-hydroxyethyl)-3-(2-methoxyphenyl)-5-methylpyrrol-2-one
• CAS: 66666-37-3
• 化学式: C₂₀H₂₄N₄O₄
• 分子量: 384.435
• InChiKey: VRACHLZMWRIGGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  121.8
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ²-pyrrolin-5-one 、 乙酸酐 以57%的产率得到
  参考文献：
  名称：

  TAKAMIZAWA A.; HARADA H.; MAKINO I., CHEM. AND PHARM. BULL., 1978, 26, NO 3, 722-735

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(4-amino-2-methylpyrimidin-5-yl)methyl-6-(2-hydroxyethyl)-2-(2-methoxyphenyl)-5-methyl-2,3-dihydro-4H-1,4-thiazin-3-one 在 双氧水 作用下， 以 溶剂黄146 为溶剂， 生成 1-Methyl-2-(2-methyl-4-aminopyrimidin-5-yl)methyl-4-hydroxy-4-(2-methoxyphenyl)-2-aza-8-oxabicyclo<3.3.0>-3-one 、 1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ²-pyrrolin-5-one
  参考文献：
  名称：

  Studies on pyrimidine derivatives and their related compounds. XCI. On the oxidation products of 2-substituted-1,4-thiazin-3-one derivatives.

  摘要：

  用过氧化氢处理 2-对氯苯基噻嗪硫胺（Ib）后，得到 2-羟基-2-对氯苯基噻嗪硫胺（IIb）。对苯基和甲基噻嗪硫胺（Ia 和 Ie）的类似反应产物进行了重新研究，发现它们分别是 IIb 类似物（IIa 和 IIe）。将 IIa、IIb 或 IIe 与乙酸酐反应，可得到相应的 N-(2-甲基-4-氨基嘧啶-5-基)甲基-N-(2-乙酰硫基-4-氨基-1-甲基-1-丁烯基)芳基（或甲基）草酰胺（分别为 IIIa、IIIb 或 IIIe）。用过氧化氢处理 2-邻甲苯基噻嗪硫胺（Ic）可得到 N-[1-（2-氧代-1、2-(2-甲基-4-氨基嘧啶-5-基)甲基]-N-[(2-甲基-4-氨基嘧啶-5-基)甲基]-邻甲苯基柳酰胺(VIIIc)作为主要产物，用过氧化氢处理邻甲氧基苯基噻嗪硫胺(Id)得到 1-(2-甲基-4-氨基嘧啶-5-基)甲基-2-甲基-3-(2-羟乙基)-4-羟基-4-(2-甲氧基苯基)-&lrtri；2-吡咯啉-5-酮 (XV)。用间氯过苯甲酸氧化 Ia、Ic 和 Id 还可得到 VIIIc 和相应的 VIIIc 类似物（分别为 VIIIa 和 VIIId）。这些反应的机理如图 2 所示。

  DOI：

  10.1248/cpb.26.722

文献信息

• Studies on pyrimidine derivatives and related compounds. XCIV. On the oxidation products of 2-substituted-2,3-dihydro-4H-1,4-thiazin-3-one derivatives.
  作者：AKIRA TAKAMIZAWA、HIROSHI HARADA

  DOI：10.1248/cpb.28.769

  日期：——

  Hydrogen peroxide oxidation of 4-(4-amino-2-methylpyrimidin-5-yl) methyl-6-(2-hydroxyethyl)-2-(2-methoxyphenyl)-4-methyl-2, 3-dihydro-4H-1, 4-thiazin-3-one (1c) gave N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[1-(2-oxido-1, 2-oxathiolan-3-yliden)ethyl] (2-methoxyphenyl)oxalamide (3b) and 2-oxido-1, 2-oxathiolane-3-spiro-3'-[1'-(4-amino-2-methylpyrimidin-5-yl)methyl-4'-hydroxy-2'-methylene-4'-(2-methoxyphenyl)-tetrahydropyrrol-5'-one] (6). The former product (3b) was transformed into another product (6) under oxidative reaction conditions and 6 led to the known 1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ2-pyrrolin-5-one (4) and 2-aza-2-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-4-(2-methoxyphenyl)-1-methyl-8-oxabicyclo [3.3.0] octan-3-one (5) on acid or alkali treatment. On the other hand, an oxalamide (3d) having a 2-anisyl substituent was recovered under the same reaction conditions. The same reaction with 2-aryl-4-benzyl-2, 3-dihydro-4H-1, 4-benzothiazin-3-ones (12a-c) afforded 2-aryl-4-benzyl-2-hydroxy-2, 3-dihydro-4H-1, 4-benzothiazin-3-ones (13a-c), bis-(2-aryloxalylaminophenyl)-1, 1'-disulfide (14a-b) and 2-aryl-4-benzyl-3-oxo-2, 3-dihydro-4H-1, 4-benzothiazine-1, 1-dioxide (15a-c), while 4-benzyl-2-methyl-2, 3-dihydro-4H-1, 4-benzothiazine-1, 3-dioxide (16b) was mainly obtained in the oxidation of the 2-methyl derivative (12d), which was converted into 4-benzyl-2-hydroxy-2-methyl-2, 3-dihydro-4H-1, 4-benzothiazin-3-oxide (13d) via a Pummerer-type rearrangement. The reaction mechanism is discussed.

  4-(4-氨基-2-甲基嘧啶-5-基)甲基-6-(2-羟乙基)-2-(2-甲氧基苯基)-4-甲基-2, 3-二氢-4H-1的过氧化氢氧化, 4-噻嗪-3-酮 (1c) 得到 N-[(4-氨基-2-甲基嘧啶-5-基)甲基]-N-[1-(2-oxydo-1, 2-oxathiolan-3-yliden) )乙基](2-甲氧基苯基)草酰胺(3b)和2-氧化-1, 2-氧硫杂环戊烷-3-螺-3'-[1'-(4-氨基-2-甲基嘧啶-5-基)甲基-4 '-羟基-2'-亚甲基-4'-(2-甲氧基苯基)-四氢吡咯-5'-酮](6)。前产物(3b)在氧化反应条件下转化为另一种产物(6)，6产生已知的1-(4-氨基-2-甲基嘧啶-5-基)甲基-4-羟基-3-(2-羟乙基)-4-(2-甲氧基苯基)-2-甲基-Δ2-吡咯啉-5-酮(4)和2-氮杂-2-(4-氨基-2-甲基嘧啶-5-基)甲基-4-羟基-4-(2-甲氧基苯基)-1-甲基-8-氧杂双环[3.3.0]辛烷-3-酮(5)经酸或碱处理。另一方面，在相同的反应条件下回收具有2-茴香基取代基的草酰胺(3d)。与 2-芳基-4-苄基-2, 3-二氢-4H-1, 4-苯并噻嗪-3-酮 (12a-c) 进行相同的反应，得到 2-芳基-4-苄基-2-羟基-2, 3 -二氢-4H-1, 4-苯并噻嗪-3-酮 (13a-c), 双-(2-芳基草酰基氨基苯基)-1, 1'-二硫化物 (14a-b) 和 2-芳基-4-苄基-3- oxo-2, 3-二氢-4H-1, 4-苯并噻嗪-1, 1-二氧化物 (15a-c)，而 4-苄基-2-甲基-2, 3-二氢-4H-1, 4-苯并噻嗪- 1, 3-二氧化物(16b)主要是在2-甲基衍生物(12d)氧化过程中得到，转化为4-苄基-2-羟基-2-甲基-2, 3-二氢-4H-1，通过普默勒型重排得到 4-苯并噻嗪-3-氧化物 (13d)。讨论了反应机理。