methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide | 243636-63-7

• 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: methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide
• 英文别名: methyl 3-[[(E)-but-2-enyl]-[(3,4-dimethoxyphenyl)methyl]amino]-3-oxopropanoate
• CAS: 243636-63-7
• 化学式: C₁₇H₂₃NO₅
• 分子量: 321.373
• InChiKey: TVKJFVYLKANFIN-AATRIKPKSA-N

物化性质

• 沸点：
  456.2±45.0 °C(Predicted)
• 密度：
  1.118±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide 在 palladium diacetate tetraphosphorus decasulfide 、 硫酸 、 copper diacetate 、 manganese triacetate 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 生成 N-(4-(2-(2-氨基-4-氧代-4,7-二氢-3H-吡咯并[2,3-d]嘧啶-5-基)乙基)苯甲酰基)-L-谷氨酸二乙酯
  参考文献：
  名称：

  抗肿瘤药LY231514（MTA）7-取代衍生物的新颖合成途径

  摘要：

  This paper describes a further synthesis of the pyrrolo[2,3-d]pyrimidine antitumor agent MTA (LY231514). Manganic triacetate dihydrate-induced radical cyclization of methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide (4d) yielded the 3-carbomethoxy-2-pyrrolidinone 5d that was then thiated with P2S5 to the corresponding thiolactam (6d). Cyclization with guanidine gave the 7-substituted 2-amino-4(3H)-oxo5,6-dihydro-pyrrolo[2,3-d]pyrimidine (7d). Pd-catalyzed coupling with diethyl 4-iodobenzoylglutamate yielded (in a single step) the diethyl ester 9d. Deprotection with H2SO4/TFA followed by saponification then gave MTA. Several additional 7-substituted derivatives of MTA were prepared by use of this methodology. In contradiction to a published claim, these 7-substituted derivatives proved to be devoid of any significant cell growth inhibitory activity. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00959-4
• 作为产物：
  描述：

  methyl N-(3',4'-dimethoxybenzyl)carbamate 在 氢氧化钾 、 一水合肼 作用下， 反应 2.0h， 生成 methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide
  参考文献：
  名称：

  抗肿瘤药LY231514（MTA）7-取代衍生物的新颖合成途径

  摘要：

  This paper describes a further synthesis of the pyrrolo[2,3-d]pyrimidine antitumor agent MTA (LY231514). Manganic triacetate dihydrate-induced radical cyclization of methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide (4d) yielded the 3-carbomethoxy-2-pyrrolidinone 5d that was then thiated with P2S5 to the corresponding thiolactam (6d). Cyclization with guanidine gave the 7-substituted 2-amino-4(3H)-oxo5,6-dihydro-pyrrolo[2,3-d]pyrimidine (7d). Pd-catalyzed coupling with diethyl 4-iodobenzoylglutamate yielded (in a single step) the diethyl ester 9d. Deprotection with H2SO4/TFA followed by saponification then gave MTA. Several additional 7-substituted derivatives of MTA were prepared by use of this methodology. In contradiction to a published claim, these 7-substituted derivatives proved to be devoid of any significant cell growth inhibitory activity. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00959-4

文献信息

• A novel synthetic route to 7-substituted derivatives of the antitumor agent LY231514 (MTA)
  作者：Edward C. Taylor、Bin Liu

  DOI：10.1016/s0040-4039(99)00959-4

  日期：1999.7

  This paper describes a further synthesis of the pyrrolo[2,3-d]pyrimidine antitumor agent MTA (LY231514). Manganic triacetate dihydrate-induced radical cyclization of methyl N-crotyl-N-(3',4'-dimethoxybenzyl)malonamide (4d) yielded the 3-carbomethoxy-2-pyrrolidinone 5d that was then thiated with P2S5 to the corresponding thiolactam (6d). Cyclization with guanidine gave the 7-substituted 2-amino-4(3H)-oxo5,6-dihydro-pyrrolo[2,3-d]pyrimidine (7d). Pd-catalyzed coupling with diethyl 4-iodobenzoylglutamate yielded (in a single step) the diethyl ester 9d. Deprotection with H2SO4/TFA followed by saponification then gave MTA. Several additional 7-substituted derivatives of MTA were prepared by use of this methodology. In contradiction to a published claim, these 7-substituted derivatives proved to be devoid of any significant cell growth inhibitory activity. (C) 1999 Elsevier Science Ltd. All rights reserved.