tert-butyl 3-(2-hydroxyethyl)-1H-indole-1-carboxylate | 141972-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 3-(2-hydroxyethyl)-1H-indole-1-carboxylate
• 英文别名: tert-butyl 3-(2-hydroxyethyl)indole-1-carboxylate
• CAS: 141972-32-9
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: VTFPZEDGWAEVDL-UHFFFAOYSA-N

物化性质

• 沸点：
  403.4±37.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2-hydroxyethyl)-1H-indole-1-carboxylate 在 1,3-二溴-5,5-二甲基海因 、 C₄₀H₅₈CoN₂O₆^(1-)*H⁽¹⁺⁾ 作用下， 以 四氯化碳 、 甲苯 为溶剂， 反应 48.0h， 以95%的产率得到(3aR,8aS)-tert-butyl 3a-bromo-3,3a-dihydro-2H-furo[2,3-b]indole-8(8aH)-carboxylate
  参考文献：
  名称：

  Enantioselective Halocyclization of Indole Derivatives: Using 1,3-Dihalohydantoins with Anionic Chiral Co(III) Complexes

  摘要：

  摘要：利用阴离子手性Co（III）配合物和1,3-二卤代海因杜因（仅需0.50当量）实现了吲哚衍生物的高度对映选择性卤环化反应，包括色氨酸醇和色氨酸胺。采用手性阴离子相转移催化策略，得到了3-卤代融合吲哚烷，收率高（高达98％）和对映选择性高（高达98％ee）。

  DOI：

  10.1055/a-1310-5213
• 作为产物：
  描述：

  甲基吲哚-3-乙酸盐 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 8.0h， 生成 tert-butyl 3-(2-hydroxyethyl)-1H-indole-1-carboxylate
  参考文献：
  名称：

  邻羰基辅助的金催化乙酸丙炔酯的区域选择性水合：获得α-酰氧基甲基酮和（±）-Actinopolymorphol B的合成†

  摘要：

  通过范围广泛的乙酸炔丙酯的区域选择性水合证明了合成α-酰氧基甲基酮的一般的原子经济方法。在二恶烷-H 2 O中包含1％Ph 3 PAuCl和1％AgSbF 6的现成催化剂可在短时间内在环境温度下在短短时间内有效地水解炔丙基乙酸酯的末端炔烃。如18所示，相邻的羰基可促进有效的区域选择性水化O标记研究。观察到功能部分的相容性和对各种酸不稳定的保护基的耐受性。催化条件也适合于进行TMS取代的炔丙基乙酸酯的水合作用，即使需要更长的反应时间才能完成。在水合过程中保留了炔丙基乙酸酯的立体完整性。通过以几乎定量的产量进行克规模的产品制备，成功地证明了该系统的鲁棒性。普通的α-酰氧基甲基酮被转化为1,2-二醇和1,2-氨基醇衍生物。肌动蛋白多酚B的合成首次实现，其中乙酸炔丙基酯的水合是关键步骤。

  DOI：

  10.1021/jo101995g

文献信息

• An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
  作者：Jun Xu、Rongbiao Tong

  DOI：10.1039/c7gc01341h

  日期：——

  environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing

  开发了一种环境友好，高效的方案，用于色胺/色氨酸衍生物的氧化卤代环化反应，并通过28个实例进行了证明，并简明地合成了环色胺生物碱A和B的全合成。与所有先前方法相比，该方案的独特优势在于：卤化剂或氧化剂不会产生有机副产物，因此大大降低了卤代环化对环境的影响，并促进了反应后的纯化。
• Cooperativity within the catalyst: alkoxyamide as a catalyst for bromocyclization and bromination of (hetero)aromatics
  作者：Haripriyo Mondal、Md Raja Sk、Modhu Sudan Maji

  DOI：10.1039/d0cc04673f

  日期：——

  Alkoxyamide has been reported as a catalyst for the activation of N-bromosuccinimide to perform bromocyclization and bromination of a wide range of substrates in a lipophilic solvent, where adequate suppression of the background reactions was observed. The key feature of the active site is the alkoxy group attached to the sulfonamide moiety, which facilitates the acceptance as well as the delivery

  据报道，烷氧基酰胺是一种催化剂，用于在亲脂性溶剂中活化N-溴琥珀酰亚胺来进行溴化和各种底物的溴化反应，并观察到对本底反应的充分抑制。活性位点的关键特征是连接至磺酰胺部分的烷氧基，这有助于将溴物种从溴源接收到基质以及从基质向基质的传递。
• [EN] 2 -MORPHOLINOPYRIMIDINES AND THEIR USE AS PI3 KINASE INHIBITORS<br/>[FR] 2-MORPHOLINOPYRIMIDINES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE PI3
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009066084A1

  公开（公告）日：2009-05-28

  Morpholino pyrimidines of formula (I): wherein R1 is selected from -Y-R6 and -NR4R5; R2 is a N-containing monocyclic heteroaryl group which is selected from pyridyl, isoxazolyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxazolyl, furanyl, thienyl, triazolyl and tetrazolyl and which is unsubstituted or substituted by halo, -CN, -NR10R11, -OR10, -C(O)R10, -NR10C(O)R11, - N(C(O)R11)2, -NR10C(O)NR10R11, -SO2R10R11, -SO2NR10R11, -C(=O)OR10, -C(=O)NR10R11, halo-C1 -C6 alkyl and unsubstituted C1-C12 alkyl; R3 is selected from H, C1-C6 alkyl and C1-C6 alkoxy; Y is selected from a direct bond, -(CR2)m-, C2-C6 alkenylene, C2-C6 alkynylene, -(CR2)p-O-(CR2) t-, -(CR2)p-NR-(CR2) t, -(CR2)p-NR-(CR2)n-C(O)-, -(CR2)p-NR-C(O)- (CR2)n-, -(CR2)p-C(O)-NR-(CR2) t, -(CR2)p-C(O)-(CR2)n-NR-(CR2)t,- and -(CR2)p- C(O)-(CR2)n-; R6 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic ring, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted, C1-C6 alkyl, -NR2, -OR, -NR(CO)R and - C(O)NR2; R4 and R5, which are the same or different, are both C1-C6 alkyl which is unsubstituted or substituted, or R4 and R5 together form, with the nitrogen atom to which they are attached, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted; each R, which are the same or different when more than one is present in a given group, is independently H, C1-C6 alkyl which is unsubstituted or substituted or a 5- to 12-membered aryl or heteroaryl group which is unsubstituted or substituted; R10 and R11, which are the same or different, are independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C3-C8 cycloalkyl; n is 0 or an integer of 1 to 6; m is an integer of 1 to 6; p is 0 or an integer of 1 to 6; and t is 0 or an integer of 1 to 6, with the proviso that t is an integer of 2 to 6 when R6 is linked to Y through a constituent O or N atom of R6; and the pharmaceutically acceptable salts thereof, subject to various provisos, have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour, particularly that associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式(I)的吗哥啉嘧啶，其中R1从-Y-R6和-NR4R5中选择；R2是一种含氮的单环杂环芳基，选择自吡啶基、异噁唑基、咪唑基、吡唑基、吡咯基、噻唑基、吡啶嗪基、嘧啶基、吡嗪基、噁唑基、呋喃基、噻吩基、三唑基和四唑基，未取代或取代为卤素、-CN、-NR10R11、-OR10、-C(O)R10、-NR10C(O)R11、-N(C(O)R11)2、-NR10C(O)NR10R11、-SO2R10R11、-SO2NR10R11、-C(=O)OR10、-C(=O)NR10R11、卤代-C1-C6烷基和未取代的C1-C12烷基；R3从H、C1-C6烷基和C1-C6烷氧基中选择；Y从直接键、-(CR2)m-、C2-C6烯基、C2-C6炔基、-(CR2)p-O-(CR2)t-、-(CR2)p-NR-(CR2)t、-(CR2)p-NR-(CR2)n-C(O)-、-(CR2)p-NR-C(O)-(CR2)n-、-(CR2)p-C(O)-NR-(CR2)t、-(CR2)p-C(O)-(CR2)n-NR-(CR2)t和-(CR2)p-C(O)-(CR2)n-中选择；R6从未饱和的5-至12成员碳环或杂环环中选择，饱和的5、6或7成员N含杂环基，未取代或取代，C1-C6烷基，-NR2，-OR，-NR(CO)R和-C(O)NR2中选择；R4和R5，相同或不同，均为未取代或取代的C1-C6烷基，或R4和R5与它们连接的氮原子形成未取代或取代的饱和的5、6或7成员N含杂环基；每个R，当在给定的基团中存在多个时，相同或不同，独立地为H，未取代或取代的C1-C6烷基或未取代或取代的5-至12成员芳基或杂环基；R10和R11，相同或不同，独立地选择自H，C1-C6烷基，C2-C6烯基，C2-C6炔基和C3-C8环烷基；n为0或1至6的整数；m为1至6的整数；p为0或1至6的整数；t为0或1至6的整数，但当R6通过R6的一个成分O或N原子与Y连接时，t为2至6的整数；以及其药学上可接受的盐，受各种规定限制，具有PI3K抑制剂的活性，因此可用于治疗由于异常细胞生长、功能或行为引起的疾病和紊乱，特别是与PI3激酶相关的癌症、免疫紊乱、心血管疾病、病毒感染、炎症、代谢/内分泌紊乱和神经系统紊乱。还描述了合成这些化合物的方法。
• Reduction of 1-pyrrolyl and 1-indolyl carbamates to hemiaminals
  作者：He-Chu Hsu、Duen-Ren Hou

  DOI：10.1016/j.tetlet.2009.10.025

  日期：2009.12

  Hemiaminals of pyrroles and indoles have been prepared from the lithium aluminum hydride reduction of 1-pyrrolyl and 1-indolyl carbamates with good yields (67–82%). These carbamates are more reactive than aliphatic amides and carbamates under the LAH reduction, but less reactive than esters.

  氢化铝和1-吡咯基和1-吲哚基氨基甲酸酯的锂铝氢化物制备了吡咯和吲哚的缩醛，收率很好（67-82％）。在LAH还原下，这些氨基甲酸酯比脂族酰胺和氨基甲酸酯具有更高的反应性，但与酯相比则具有较低的反应性。
• Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
  作者：Long Han、Chuan Liu、Wei Zhang、Xiao-Xin Shi、Shu-Li You

  DOI：10.1039/c3cc47921h

  日期：——

  An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.

  通过衍生自C2对称双异羟肟酸（BHA）配体的手性钒催化剂实现了对三酚的对映选择性环氧化，然后进行了分子内环氧化物开环反应。在温和的反应条件下获得了产率高达89％和ee达90％的3a-羟基呋喃二氢吲哚衍生物。