ethyl 1-(methylcarbamoyl)-5-aminoimidazole-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1-(methylcarbamoyl)-5-aminoimidazole-4-carboxylate
• 英文别名: Ethyl 5-amino-1-(methylcarbamoyl)imidazole-4-carboxylate
• 化学式: C₈H₁₂N₄O₃
• 分子量: 212.208
• InChiKey: WKXGRTGAGUXVDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-(methylcarbamoyl)-5-aminoimidazole-4-carboxylate 在 溶剂黄146 、 lithium chloride 、 sodium nitrite 作用下， 反应 12.0h， 以54%的产率得到ethyl 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate
  参考文献：
  名称：

  一种替莫唑胺的制备方法

  摘要：

  本发明公开了一种替莫唑胺的制备方法，包括：N‑甲基脲与甲酰化试剂进行甲酰化反应，得到N‑甲基‑N’‑甲酰基脲，使其与2‑氨基‑2‑氰基乙酸乙酯在酸和溶剂体系中进行环化反应，得到1‑(甲基氨基甲酰基)‑5‑氨基咪唑‑4‑甲酸乙酯；再使其进行重氮化作用和环化的协同反应，得到3,4‑二氢‑3‑甲基‑4‑氧代咪唑并[5,1‑d]‑1,2,3,5‑四嗪‑8‑甲酸乙酯，进而与酰胺化试剂的溶液在催化剂的条件下进行酰胺化反应，得到替莫唑胺；该方法能够在较温和的反应条件下获得理想的收率和纯度，减少了副反应的发生，后处理较简单，同时所采用试剂原料更价廉易得、安全、环保，适于工业化大规模生产。

  公开号：

  CN111233871B
• 作为产物：
  描述：

  4-氨基-1H-咪唑-5-羧酸乙酯 、 异氰酸甲酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以59%的产率得到ethyl 1-(methylcarbamoyl)-5-aminoimidazole-4-carboxylate
  参考文献：
  名称：

  Antitumor Imidazotetrazines. 35. New Synthetic Routes to the Antitumor Drug Temozolomide

  摘要：

  Three new pathways to the antitumor drug temozolomide (4) have been explored via intermediates 3, 6, and 7. The key intermediate 5-amino-1-(N-methylcarbamoyl)imidazole-4-carboxamide (6) has been successfully converted to 4 in 45% yield by employing sodium nitrite in aqueous tartaric acid at 0-5 degrees C, Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) and either methyl isocyanate or N-methylcarbamoyl chloride. Temozolomide (4) is also prepared from 8-cyano-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (7) by hydrolysis to the hydrochloride salt of 4 in 10 M hydrochloric acid. Compound 7 is prepared from either 5-diazoimidazole-4-carbonitrile (28) and methyl isocyanate or by diazotization of 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (25). Attempts to cyclize 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3) with phosgene or phosgene equivalents were unsuccessful: only 2-azahypoxanthine (11) was isolated.

  DOI：

  10.1021/jo970802l

文献信息

• 一种替莫唑胺的制备方法
  申请人：江苏美迪克化学品有限公司

  公开号：CN111233871B

  公开（公告）日：2021-11-12

  本发明公开了一种替莫唑胺的制备方法，包括：N‑甲基脲与甲酰化试剂进行甲酰化反应，得到N‑甲基‑N’‑甲酰基脲，使其与2‑氨基‑2‑氰基乙酸乙酯在酸和溶剂体系中进行环化反应，得到1‑(甲基氨基甲酰基)‑5‑氨基咪唑‑4‑甲酸乙酯；再使其进行重氮化作用和环化的协同反应，得到3,4‑二氢‑3‑甲基‑4‑氧代咪唑并[5,1‑d]‑1,2,3,5‑四嗪‑8‑甲酸乙酯，进而与酰胺化试剂的溶液在催化剂的条件下进行酰胺化反应，得到替莫唑胺；该方法能够在较温和的反应条件下获得理想的收率和纯度，减少了副反应的发生，后处理较简单，同时所采用试剂原料更价廉易得、安全、环保，适于工业化大规模生产。
• Antitumor Imidazotetrazines. 35. New Synthetic Routes to the Antitumor Drug Temozolomide
  作者：Yongfeng Wang、Malcolm F. G. Stevens、Tze-ming Chan、Donald DiBenedetto、Zhe-xing Ding、Dinesh Gala、Donald Hou、Max Kugelman、William Leong、Shen-chun Kuo、Janet L. Mas、Doris P. Schumacher、Bruce P. Shutts、Lyman Smith、Zheng-Yun J. Zhan、William T. Thomson

  DOI：10.1021/jo970802l

  日期：1997.10.1

  Three new pathways to the antitumor drug temozolomide (4) have been explored via intermediates 3, 6, and 7. The key intermediate 5-amino-1-(N-methylcarbamoyl)imidazole-4-carboxamide (6) has been successfully converted to 4 in 45% yield by employing sodium nitrite in aqueous tartaric acid at 0-5 degrees C, Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) and either methyl isocyanate or N-methylcarbamoyl chloride. Temozolomide (4) is also prepared from 8-cyano-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (7) by hydrolysis to the hydrochloride salt of 4 in 10 M hydrochloric acid. Compound 7 is prepared from either 5-diazoimidazole-4-carbonitrile (28) and methyl isocyanate or by diazotization of 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (25). Attempts to cyclize 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3) with phosgene or phosgene equivalents were unsuccessful: only 2-azahypoxanthine (11) was isolated.