3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione | 159135-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione
• 英文别名: 1-(bromomethyl)-3,4,4-trimethyl-2,5-imidazolidinedione；3-bromomethyl-1,5,5-trimethylhydantoin；1-(bromomethyl)-3,4,4-trimethyl-2,5-imidazolinedione；3-(bromomethyl)-1,5,5-trimethylimidazolidine-2,4-dione
• CAS: 159135-61-2
• 化学式: C₇H₁₁BrN₂O₂
• 分子量: 235.081
• InChiKey: BBKDOFXVZYMKAC-UHFFFAOYSA-N

物化性质

• 熔点：
  87 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  242.0±42.0 °C(Predicted)
• 密度：
  1.502±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-[2(R)-[1(R)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl]piperidine
  参考文献：
  名称：

  Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)

  摘要：

  A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid-and osteoarthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00416-2
• 作为产物：
  描述：

  1,5,5-三甲基海因 、 聚合甲醛 在 氢溴酸 、 溶剂黄146 作用下， 反应 6.0h， 以89%的产率得到3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione
  参考文献：
  名称：

  N-酰基胺离子的级联α-氧代-酰胺烷基化/转位/p-阳离子环化在合成新型稠合杂环N，O-缩醛中的应用

  摘要：

  三环 N,O-缩醛支架已从廉价试剂开始，以中等至良好的产率 (40-68%) 开始，只需几个步骤即可轻松制备，其中 α-羟基内酰胺中间体构成关键底物。这些环化产物是氧原子对内环 N-acyliminium 离子中间体的独家分子内攻击的结果，导致新的环状氮杂-氧鎓盐，它们打开成环外 N-acyliminium 物质，然后进行分子内芳基化。在这些研究中，讨论了还原和环化过程中的高化学选择性，并明确确认了环化产物的结构。

  DOI：

  10.3998/ark.5550190.0011.805
• 作为试剂：
  描述：

  3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione 、 1-O,2-O-dibenzyl 1-O-tert-butyl (2R)-3-(cyclopenten-1-yl)propane-1,1,2-tricarboxylate 在 3-bromomethyl-1,5,5-trimethylimidazolidine-2,4-dione 作用下， 以99的产率得到1-O,2-O-dibenzyl 1-O-tert-butyl (2R)-3-(cyclopenten-1-yl)-1-[(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)methyl]propane-1,1,2-tricarboxylate
  参考文献：
  名称：

  Tetrahedron 2001, 57, 7675-7683

  摘要：

  DOI：

文献信息

• Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases
  申请人：Novartis AG

  公开号：US06410580B1

  公开（公告）日：2002-06-25

  Compounds of formula (I) wherein W is —OH or —NHOH; X is an optionally substituted heterocycle, NR1SO2R2, heterocyclylalkythio, CONR2R3 or NR1COR2; Y, Z, R1-R3 and n are as defined in the application. Compounds (I) are inhibitors of matrix-degrading metalloproteinases and are use for the treatment of related conditions.

  式（I）中的化合物，其中W为—OH或—NHOH；X为可选择取代的杂环、NR1SO2R2、杂环烷硫基、CONR2R3或NR1COR2；Y、Z、R1-R3和n的定义如申请中所述。化合物（I）是基质降解金属蛋白酶的抑制剂，用于治疗相关疾病。
• Practical approaches to the matrix metalloproteinase inhibitor Trocade® (Ro 32-3555) and to the TNF-α converting enzyme inhibitor Ro 32-7315
  作者：Hans Hilpert

  DOI：10.1016/s0040-4020(01)00720-7

  日期：2001.9

  Stereoselective methods were found to efficiently prepare 2- and 3-substituted succinates with anti configuration. In the synthesis of Trocade®1, the hydantoinmethyl residue was introduced by alkylation of the non-chelated potassium enolate 19 with the bromomethyl hydantoin 9 to give a 92:8 mixture favouring the 2,3-anti configurated succinate 18. The preparation of TNF-α converting enzyme (TACE) inhibitor

  发现立体选择性方法可以有效地制备具有反构型的2-和3-取代的琥珀酸酯。在TROCADE的合成® 1中，hydantoinmethyl残余物通过非螯合钾烯醇化物烷基化引入19与溴甲基乙内酰脲9，得到92:8混合物利于2,3-反可配置琥珀酸盐18。TNF-α转化酶（TACE）抑制剂2的制备是通过使用CF 3 CONH 2对二烷基化的烯醇化物23进行高度立体选择性质子化，从而提供98：2的混合物（有利于2,3-）防琥珀酸24。
• Process for the preparation of hydroxamic acid derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06452010B1

  公开（公告）日：2002-09-17

  The present invention provides an improved process for preparing an hydroxycarbamoyl derivative of a carboxylic acid using a hydroxylammonium salt of a carboxylic acid as a reagent.

  本发明提供了一种改进的制备羧酸的羟基氨基甲酰衍生物的方法，使用羧酸的羟胺盐作为试剂。
• Hydroxamic acid derivatives with tricyclic substitution for treating
  申请人：Hoffmann-La Roche Inc.

  公开号：US05710167A1

  公开（公告）日：1998-01-20

  The invention provides hydroxamic acid derivatives of the general formula ##STR1## wherein R.sup.1 represents cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R.sup.2 represents a saturated 5- to 8-membered monocyclic or bridged N-heterocyclic ring, which N-heterocyclic ring is attached via the N atom and when it is monocyclic, optionally contains NR.sup.4, O, S, SO or SO.sub.2 as a ring member and/or is optionally substituted on one or more C atoms by hydroxy, lower alkyl, lower alkoxy, oxo, ketalized oxo, amino, mono(lower alkyl)amino, di(lower alkyl)amino, carboxy, lower alkoxycarbonyl, hydroxy-methyl, lower alkoxymethyl, carbamoyl, mono(lower alkyl)-carbamoyl, di(lower alkyl)carbamoyl or hydroxy-imino; R.sup.3 represents a 5- or 6-membered N-heterocyclic ring which (a) is attached via the N atom, (b) optionally contains N, O and/or S, SO or SO.sub.2 as an additional ring member, (c) is substituted by oxo on one or both C atoms adjacent to the linking N atom and (d) is optionally benz-fused or optionally substituted on one or more other C atoms by lower alkyl or oxo and/or on any additional N atom(s) by lower alkyl or aryl; R.sup.4 represents hydrogen, lower alkyl, aryl, aralkyl or a protecting group; m stands for 1 or 2 and n stands for 1-4, pharmaceutically acceptable salts thereof, intermediates used in the manufacture thereof, and methods of use therefor. Compounds of formula I are collagenase inhibitors useful in the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis or in the treatment of invasive tumours, atherosclerosis or multiple sclerosis.

  该发明提供了一般式为##STR1##的羟肟酸衍生物，其中R.sup.1代表环丙基，环丁基，环戊基或环己基；R.sup.2代表饱和的5-至8-成员单环或桥环N-杂环，该N-杂环通过N原子连接，当它是单环时，可选地包含NR.sup.4，O，S，SO或SO.sub.2作为环成员和/或在一个或多个C原子上可选地被羟基，较低烷基，较低烷氧基，氧代，酮化的氧代，氨基，单（较低烷基）氨基，二（较低烷基）氨基，羧基，较低烷氧羰基，羟甲基，较低烷氧甲基，氨基甲酰基，单（较低烷基）氨基甲酰基，二（较低烷基）氨基甲酰基或羟基亚胺基取代；R.sup.3代表5-或6-成员N-杂环，它（a）通过N原子连接，（b）可选地包含N，O和/或S，SO或SO.sub.2作为额外的环成员，（c）在与连接N原子相邻的一个或两个C原子上被氧代取代，（d）可选地苯并或在一个或多个其他C原子上被较低烷基或氧代取代，并且/或在任何额外的N原子上被较低烷基或芳基取代；R.sup.4代表氢，较低烷基，芳基，芳基烷基或保护基；m代表1或2，n代表1-4，它们的药学上可接受的盐，用于制造它们的中间体以及使用它们的方法。式I的化合物是胶原酶抑制剂，对于控制或预防退行性关节疾病如类风湿性关节炎和骨关节炎或治疗侵袭性肿瘤，动脉粥样硬化或多发性硬化症非常有用。
• Process for manufacturing 1-[3-cyclopentyl
  申请人：Hoffmann-La Roche Inc.

  公开号：US06031103A1

  公开（公告）日：2000-02-29

  A process manufactures of a compound of formula: ##STR1## and unique intermediates.

  一个过程制造了一个化合物的公式：##STR1## 和独特的中间体。