4,6-dichloro-2-((methylthio)pyrimidin-5-yl)(phenyl)-methanol | 1137576-47-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4,6-dichloro-2-((methylthio)pyrimidin-5-yl)(phenyl)-methanol
• 英文别名: (4,6-Dichloro-2-(methylthio)pyrimidin-5-yl)(phenyl)methanol；(4,6-dichloro-2-methylsulfanylpyrimidin-5-yl)-phenylmethanol
• CAS: 1137576-47-6
• 化学式: C₁₂H₁₀Cl₂N₂OS
• 分子量: 301.196
• InChiKey: PRJBVBOSTCNDRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-2-((methylthio)pyrimidin-5-yl)(phenyl)-methanol 在 manganese(IV) oxide 、 偶氮二甲酸二异丙酯 、 一水合肼 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 6.0h， 生成 4-chloro-1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  探索特权吡唑并[3,4- d ]嘧啶支架周围的化学空间：寻求新型的T315I突变型Abl的变构抑制剂

  摘要：

  具有高水平分子多样性的吡唑并[3,4- d ]嘧啶文库已通过应用允许C3，N1，C4和C6取代的合成序列开发而成。对这种基于“特权支架”的化合物集合的酶促筛选，证实了在以目标为导向的合成为特征的领域中，以多样性为导向的方法的使用。实际上，几种化合物对选定的激酶表现出高活性（即Src，Abl wt和T315I突变形式），而且有趣的是，新化合物作为A315的T315I突变形式的变构抑制剂出现了，打开了大门。开发新型非竞争性Abl抑制剂（T315I）的新机会。

  DOI：

  10.1021/co500004e
• 作为产物：
  描述：

  4,6-二羟基-2-甲硫基嘧啶 在 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 13.5h， 生成 4,6-dichloro-2-((methylthio)pyrimidin-5-yl)(phenyl)-methanol
  参考文献：
  名称：

  探索特权吡唑并[3,4- d ]嘧啶支架周围的化学空间：寻求新型的T315I突变型Abl的变构抑制剂

  摘要：

  具有高水平分子多样性的吡唑并[3,4- d ]嘧啶文库已通过应用允许C3，N1，C4和C6取代的合成序列开发而成。对这种基于“特权支架”的化合物集合的酶促筛选，证实了在以目标为导向的合成为特征的领域中，以多样性为导向的方法的使用。实际上，几种化合物对选定的激酶表现出高活性（即Src，Abl wt和T315I突变形式），而且有趣的是，新化合物作为A315的T315I突变形式的变构抑制剂出现了，打开了大门。开发新型非竞争性Abl抑制剂（T315I）的新机会。

  DOI：

  10.1021/co500004e

文献信息

• Regio- and Chemoselective Metalation of Chloropyrimidine Derivatives with TMPMgCl⋅LiCl and TMP₂Zn⋅2 MgCl₂⋅2 LiCl
  作者：Marc Mosrin、Paul Knochel

  DOI：10.1002/chem.200801831

  日期：2009.1.26

  Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 °C) by using TMPMgCl⋅LiCl and TMP2Zn⋅2 MgCl2⋅2 LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51–93 % yield. Oxidative aminations

  高效浸锌和氯化嘧啶的镁化可以在方便的温度下（例如，25和55℃），通过使用TMPMgCl⋅LiCl和TMP进行2 Zn⋅2 中号GCL 2 ⋅2的LiCl（TMP = 2,2,6,6-四甲基哌啶基）作为有效碱。用各种亲电试剂对所得的锌化或镁化的嘧啶进行淬灭，可提供高度官能化的嘧啶，收率为51-93％。进行氧化胺化，从而导致胺化嘧啶。通过使用这种方法，我们还制备了与药物相关的吡唑并嘧啶和杀真菌剂Mepanipyrim。
• A Facile Synthesis of 1,4-Dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one Derivatives from 4,6-Dichloro-2-(methylsulfanyl)pyrimidine
  作者：Kazuhiro Kobayashi、Yuka Tsunomori、Takashi Nogi、Hidetaka Hiyoshi、Kazuto Umezu

  DOI：10.3987/com-18-13879

  日期：——

  A facile three-step sequence has been developed for the preparation of 1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives from 4,6-dichloro2-(methylsulfanyl)pyrimidine (DCSMP) under mild conditions. Thus, the starting material is treated with LDA to generate the 5-lithiated compound, which is then allowed to react with (het)aromatic and aliphatic aldehydes to give the corresponding 144,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]alkan-l-ols. The reaction of these compounds with primary amines in the presence of triethylamine gives 144-(alkylamino)-6-chloro-2-(methylsulfanyepyrimidin-5-yl]alkan-l-ols, of which subjection to successive treatment with an equimolar amount each of sodium hydride and ethyl chloroformate provides the desired 1,4-disubstituted 7-(methylsulfany1)-1,4-dihydro-2H-pyrimido [4,5-d] [1,3]oxazin-2-ones.
• Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors
  作者：Cristina Tintori、Giuseppina La Sala、Giulia Vignaroli、Lorenzo Botta、Anna Lucia Fallacara、Federico Falchi、Marco Radi、Claudio Zamperini、Elena Dreassi、Lucia Dello Iacono、Donata Orioli、Giuseppe Biamonti、Mirko Garbelli、Andrea Lossani、Francesca Gasparrini、Tiziano Tuccinardi、Ilaria Laurenzana、Adriano Angelucci、Giovanni Maga、Silvia Schenone、Chiara Brullo、Francesca Musumeci、Andrea Desogus、Emmanuele Crespan、Maurizio Botta

  DOI：10.1021/acs.jmedchem.5b00140

  日期：2015.6.11

  Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies,; such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with K-i of about 2 mu M, while derivative 4a, derived from our internal library, showed a K-i of 0.9 mu M. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 44 having K(i)s of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of : the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines.
• Synthesis of 8,9-Dihydropyrimido[4,5-e][1,4]oxazepin-7(5H)-ones by the Reaction of 1-(4-Chloropyrimidin-5-yl)alkan-1-ols with N-Alkylglycines
  作者：Kazuhiro Kobayashi、Takashi Nogi、Yuka Tsunomori、Hidetaka Hiyoshi、Kazuto Umezu

  DOI：10.3987/com-17-13795

  日期：——

  A facile method for the construction of a new ring system, 8,9-dihydropyrimido[4,5-e][1,4]oxazepin-7(5H)-one, is described. The key feature of the synthetic route includes substitution of one of the two chloro groups of 1-(4,6-dichloropyrimidin-5-yl)alkan-1-o1 derivatives, which can easily be derived from the reaction between 5-lithiated compound of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) and aldehydes, with N-alkylglycines in the presence of triethylamine, followed by lactonization of the resulting hydroxy acids catalyzed by in situ generated triethylamine hydrochloride.
• US7435731B2
  申请人：——

  公开号：US7435731B2

  公开（公告）日：2008-10-14