甲基2-异硫氰酸基丁酸酯 | 68693-53-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甲基2-异硫氰酸基丁酸酯
• 英文名称: 2-Isothiocyanato-butyric acid methyl ester
• 英文别名: Methyl 2-isothiocyanatobutanoate
• CAS: 68693-53-8
• 化学式: C₆H₉NO₂S
• 分子量: 159.209
• InChiKey: JQEICALGZPXFNA-UHFFFAOYSA-N

物化性质

• 沸点：
  100 °C
• 密度：
  1.11

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  对氯苯乙酮 、 甲基2-异硫氰酸基丁酸酯 在 N,N'-bis(3-methoxysalicylidene)(binaphthyl)-1,4-diamine 、 二丁基镁 作用下， 以 甲苯 为溶剂， 反应 48.0h， 以76%的产率得到(4R,5R)-methyl 5-(4-chlorophenyl)-4-ethyl-5-methyl-2-thioxooxazolidine-4-carboxylate
  参考文献：
  名称：

  通过直接催化不对称醛醇和曼尼希型反应构建连续的四取代手性碳立体中心

  摘要：

  描述了具有邻位四取代的手性碳立体中心的非天然氨基酸的催化不对称合成。在第一部分中，实现了简单的未活化的酮亲电体与α-取代的α-异硫氰酸酯供体的直接催化不对称醛醇缩合反应。镁/席夫碱催化剂促进了醛醇缩合反应，在高达98％ee和98：2 dr的条件下获得了α-氨基-β-羟基酯。第二部分，镁/席夫碱催化剂和Sr /席夫碱催化剂用于酮亚胺的立体发散性直接不对称曼尼希型反应。Mg / Schiff碱催化剂产生合成α-β-二氨基酯，而Sr / Schiff碱催化剂产生抗α-β-二氨基酯，对映选择性高至高，对比例高达97％ee。DOI 10.1002 / tcr.201100020

  DOI：

  10.1002/tcr.201100020

文献信息

• Construction of Contiguous Tetrasubstituted Chiral Carbon Stereocenters via Direct Catalytic Asymmetric Aldol Reaction of α-Isothiocyanato Esters with Ketones
  作者：Tatsuhiko Yoshino、Hiroyuki Morimoto、Gang Lu、Shigeki Matsunaga、Masakatsu Shibasaki

  DOI：10.1021/ja908571w

  日期：2009.12.2

  contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol reaction of alpha-substituted alpha-isothiocyanato esters with unactivated simple ketones is described. A Bu(2)Mg/Schiff base catalyst promoted the aldol addition/cyclization sequence at room temperature, giving protected alpha-amino-beta-hydroxy esters with contiguous tetrasubstituted chiral carbon stereocenters

  描述了通过 α-取代的 α-异硫氰酸酯与未活化的简单酮的直接催化不对称羟醛反应构建连续的四取代手性碳立体中心。Bu(2)Mg/Schiff 碱催化剂在室温下促进了羟醛加成/环化序列，得到了具有连续四取代手性碳立体中心的受保护 α-氨基-β-羟基酯，产率 99% 至 68%，产率为 98:2 至 74： 26 dr，和 98% 到 82% ee。
• A Novel Solution- and Solid-Phase Approach to 2,4,5-tri- and 2,4,5,6-tetrasubstituted pyrimidines and their conversion into condensed heterocycles
  作者：Thierry Masquelin、Daniel Sprenger、Roman Baer、Fernand Gerber、Yves Mercadal

  DOI：10.1002/hlca.19980810315

  日期：——

  and [bis(methylthio)methylidene]malononitrile (6), respectively, was first established in solution (Scheme 1) and successfully transferred onto solid support by using the polymer-bound thiouronium salt 11 (Scheme 3). Further investigations were directed toward a multidirectional cleavage procedure of the 2-(alkylsulfinyl) intermediates, obtained from the 2-(alkylthio)pyrimidines 7a (Scheme 2) or 12

  通过缩合3型硫脲盐与（乙氧基亚甲基）丙二腈的缩合反应合成2,4,5-三-和2,4,5,6-四取代的嘧啶5a-d和7a，e，f，g （4首先在溶液中（流程1）分别建立）和[双（甲硫基）亚甲基]丙二腈（6），然后使用与聚合物结合的硫代铀盐11（流程3）成功地将其转移到固体载体上。进一步的研究针对由2-（烷硫基）嘧啶7a（方案2）获得的2-（烷基亚磺酰基）中间体的多方向裂解程序）或12和14（方案3和4），用不同的亲核试剂形成高度取代的嘧啶。另外，稠合杂环衍生物22A - H，24A-C ，和26A-E在产生良好至优秀通过缩合收率7a中，E，H与多功能的异氰酸酯和异硫氰酸酯，与随后烷基化（方案5） 。
• Compounds, pharmaceutical compositions, and methods for inhibiting cyclin-dependent kinases
  申请人：——

  公开号：US20030220326A1

  公开（公告）日：2003-11-27

  Pharmaceutical compositions containing effective amounts of CDK-inhibiting diaminothiazole compounds of the following formula (where R 1 and R 2 are as defined in the specification) or their salts, or prodrugs or active metabolites of such compounds or salts, are useful for treating disorders and diseases such as cancer: 1 In preferred embodiments, R 1 and R 2 are independently unsubstituted or substituted carbocyclic or heterocyclic aryl ring structures. Compounds where R 2 is ortho-substituted aryl are especially potent inhibitors of CDKs such as CDK4.

  含有以下公式中CDK抑制二氨基噻唑化合物的有效量的药物组合物（其中R1和R2如规范所定义）或其盐，或这些化合物或盐的前药或活性代谢物，可用于治疗癌症等疾病和疾病。在首选实施例中，R1和R2分别是未取代或取代的碳环或杂环芳香环结构。其中R2为邻位取代芳香族的化合物特别是CDKs如CDK4的有效抑制剂。
• 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1215208A2

  公开（公告）日：2002-06-19

  This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.

  本发明涉及式（I）的氨基噻唑化合物，其中 R1 是一个取代或未取代的基团，选自......：C1-6-烷基；C1-6-烯基；C1-6-炔基；C1-6-烷氧基；C1-6-醇；碳环或杂环、单环或融合或不融合多环、环烷基；碳环或杂环、单环或融合或不融合多环、芳基；羰基；醚；(C1-6-烷基)-羰基；(C1-6-烷基)-芳基；(C1-6-烷基)-环烷基；(C1-6-烷基)-(C1-6-烷氧基)；芳基-(C1-6-烷氧基)；硫醚；硫醇；和磺酰基；其中，当 R1 被取代时，每个取代基独立地为卤素；卤代烷基；C1-6-烷基；C1-6-烯基；C1-6-炔基；羟基；C1-6-烷氧基；氨基；硝基；硫醇、硫醚；亚胺；氰基；氨基；膦酰基；膦；羧基；硫代羰基；磺酰基；磺酰胺；酮；醛；酯；氧；碳环或杂环、单环或有熔合或无熔合多环、环烷基；或碳环或杂环、单环或有熔合或无熔合多环、芳基；和 R2 是碳环或杂环、单环或融合或不融合多环、环状结构，在邻近连接点的位置有一个取代基，该环状结构可选择被进一步取代，其中 R2 的每个取代基独立地是卤素；卤代烷基；C1-6-烷基；C1-6-烯基；C1-6-炔基；羟基；C1-6-烷氧基；氨基；硝基；硫醇；硫醚；亚胺；氰基；氨基；膦酰基；膦；羧基；硫代羰基；磺酰基；磺酰胺；酮；醛；酯；氧；碳环或杂环、单环或有熔合或无熔合多环、环烷基；或碳环或杂环、单环或有熔合或无熔合多环、芳基；或式（I）化合物的药学上可接受的盐，或式（I）化合物或其药学上可接受的盐的原药或药学活性代谢物，用于抑制细胞周期蛋白依赖性激酶（CDKs），如 CDK1、CDK2、CDK4 和 CDK6。本发明还涉及含有此类化合物的药物组合物的治疗或预防用途，以及通过施用有效量的此类化合物治疗恶性肿瘤和其他疾病的方法。
• 4-AMINOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF CYCLIN-DEPENDENT KINASES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1056732A2

  公开（公告）日：2000-12-06