(Z)-2-(4,5-Dimethoxy-2-methyl-benzyl)-3-methoxy-acrylonitrile | 63940-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-2-(4,5-Dimethoxy-2-methyl-benzyl)-3-methoxy-acrylonitrile
• 英文别名: 1,2-Dimethoxy-4-methyl-5-(2-cyano-3-methoxy-2-propenyl)benzene；2-[(4,5-dimethoxy-2-methylphenyl)methyl]-3-methoxyprop-2-enenitrile
• CAS: 63940-81-8
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: XTVUNWCMOBKFEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基甲苯 以 甲醇 、 二甲基亚砜 为溶剂， 反应 21.5h， 生成 (Z)-2-(4,5-Dimethoxy-2-methyl-benzyl)-3-methoxy-acrylonitrile
  参考文献：
  名称：

  Syntheses of antibacterial 2,4-diamino-5-benzylpyrimidines. Ormetoprim and trimethoprim

  摘要：

  A general and mild method for the synthesis of 2,4-diamino-5-benzylpyrimidines was achieved by the Friedel-Crafts reaction between 2-(methoxymethylene)-3-methoxypropanenitrile (10) and an activated aromatic substrate followed by treatment with guanidine. The method is illustrated by a synthesis of ormetoprim (2) in 75% overall yield from 3,4-dimethoxytoluene (12). Efficient syntheses of trimethoprim (1) and 2 were also accomplished via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitriles 19 and 20, respectively, followed by condensation with guanidine. 12 was prepared from 3-bromo-4-methoxytoluene by a Cu(I)-catalyzed displacement of bromine by methoxide and 4,5-dimethoxy-2-methylbenzaldehyde was obtained from 12 in 87% yield by a pyridine-catalyzed Vilsmeier reaction using DMF-POCl3.

  DOI：

  10.1021/jo00039a006

文献信息

• Cyano-enol ethers
  申请人：Hoffmann-La Roche Inc.

  公开号：US04151196A1

  公开（公告）日：1979-04-24

  The present invention relates to a new synthesis for the preparation of 5-(substituted benzyl)-2,4-diamino-pyrimidines, including new pyrimidine derivatives. More particularly, a new synthesis of ormetoprin, diaveridine and related compounds, including novel derivatives, is disclosed. The synthesis involves the condensation of a substituted benzene and an acrylonitrile derivative to directly give enol ether intermediates, which upon subsequent reaction by known techniques with guanidine, provides the desired 5-(substituted benzyl)-2,4-diamino-pyrimidines, including novel compounds. The pyrimidine end products are useful as potentiators of sulfonamides and as antibacterial agents.

  本发明涉及一种新的合成方法，用于制备5-（取代苯基）-2,4-二氨基嘧啶，包括新的嘧啶衍生物。更具体地，揭示了ormetoprin，diaveridine和相关化合物的新合成方法，包括新颖的衍生物。该合成方法涉及将取代苯和丙烯腈衍生物缩合，直接得到烯醚中间体，随后通过已知技术与胍反应，提供所需的5-（取代苯基）-2,4-二氨基嘧啶，包括新化合物。嘧啶终产品可用作磺胺类药物的增效剂和抗菌剂。
• 2,4-Diamino-pyrimidine derivatives and processes
  申请人：Hoffman-La Roche Inc.

  公开号：US04033962A1

  公开（公告）日：1977-07-05

  The present invention relates to a new synthesis for the preparation of 5-(substituted benzyl)-2,4-diamino-pyrimidines, including new pyrimidine derivatives. More particularly, a new synthesis of ormetoprin, diaveridine and related compounds, including novel derivatives, is disclosed. The synthesis involves the condensation of a substituted benzene and an acrylonitrile derivative to directly give enol ether intermediates, which upon subsequent reaction by known techniques with guanidine, provides the desired 5-(substituted benzyl)-2,4-diamino-pyrimidines, including novel compounds. The pyrimidine end products are useful as potentiators of sulfonamides and as antibacterial agents.

  本发明涉及一种新的合成方法，用于制备5-（取代苯基）-2,4-二氨基嘧啶，包括新的嘧啶衍生物。更具体地，揭示了一种新的制备奥美匹林，地阿维林和相关化合物的合成方法，包括新的衍生物。该合成方法涉及将取代苯和丙烯腈衍生物缩合，直接生成烯醚中间体，随后通过已知技术与胍反应，提供所需的5-（取代苯基）-2,4-二氨基嘧啶，包括新的化合物。嘧啶终产品可用作磺胺类药物的增效剂和抗菌剂。
• Process for preparing cyano-enol ethers
  申请人：Hoffmann-La Roche Inc.

  公开号：US04108888A1

  公开（公告）日：1978-08-22

  The present invention relates to a new synthesis for the preparation of 5-(substituted benzyl)-2,4-diamino-pyrimidines, including new pyrimidine derivatives. More particularly, a new synthesis of ormetoprin, diaveridine and related compounds, including novel derivatives, is disclosed. The synthesis involves the condensation of a substituted benzene and an acrylonitrile derivative to directly give enol ether intermediates, which upon subsequent reaction by known techniques with guanidine, provides the desired 5-(substituted benzyl)-2,4-diamino-pyrimidines, including novel compounds. The pyrimidine end products are useful as potentiators of sulfonamides and as antibacterial agents.

  本发明涉及一种新的合成方法，用于制备5-(取代苯基)-2,4-二氨基嘧啶，包括新的嘧啶衍生物。更具体地，本发明揭示了ormetoprin、diaveridine和相关化合物的新合成方法，包括新的衍生物。该合成方法涉及将取代苯和丙烯腈衍生物缩合，直接得到烯醚中间体，随后通过已知技术与胍反应，得到所需的5-(取代苯基)-2,4-二氨基嘧啶，包括新的化合物。嘧啶末端产物可用作磺胺类药物的增效剂和抗菌剂。
• Syntheses of antibacterial 2,4-diamino-5-benzylpyrimidines. Ormetoprim and trimethoprim
  作者：Percy S. Manchand、Perry Rosen、Peter S. Belica、Gloria V. Oliva、Agostino V. Perrotta、Harry S. Wong

  DOI：10.1021/jo00039a006

  日期：1992.6

  A general and mild method for the synthesis of 2,4-diamino-5-benzylpyrimidines was achieved by the Friedel-Crafts reaction between 2-(methoxymethylene)-3-methoxypropanenitrile (10) and an activated aromatic substrate followed by treatment with guanidine. The method is illustrated by a synthesis of ormetoprim (2) in 75% overall yield from 3,4-dimethoxytoluene (12). Efficient syntheses of trimethoprim (1) and 2 were also accomplished via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitriles 19 and 20, respectively, followed by condensation with guanidine. 12 was prepared from 3-bromo-4-methoxytoluene by a Cu(I)-catalyzed displacement of bromine by methoxide and 4,5-dimethoxy-2-methylbenzaldehyde was obtained from 12 in 87% yield by a pyridine-catalyzed Vilsmeier reaction using DMF-POCl3.