N-[3,5-双（三氟甲基）苯基]-N''-[（1R，2R）-2-（1,3-二氢-2H-异吲哚-2-基）环己基]硫脲 | 620960-27-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[3,5-双（三氟甲基）苯基]-N''-[（1R，2R）-2-（1,3-二氢-2H-异吲哚-2-基）环己基]硫脲
• 中文别名: N-[3,5-双(三氟甲基)苯基]-N'-[(1R,2R)-2-(1,3-二氢-2H-异吲哚-2-基)环己基]硫脲
• 英文名称: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-(isoindolin-2-yl)cyclohexyl)thiourea
• 英文别名: N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1R,2R)-2-(1,3-dihydro-2H-isoindol-2-yl)cyclohexyl]thiourea；1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-(1,3-dihydroisoindol-2-yl)cyclohexyl]thiourea
• CAS: 620960-27-2
• 化学式: C₂₃H₂₃F₆N₃S
• 分子量: 487.512
• InChiKey: KIDBBKIWFZMJNT-WOJBJXKFSA-N

物化性质

• 熔点：
  154-156 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  468.9±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-((1R,2R)-2-aminocyclohexyl)isoindoline-1,3-dione 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 32.0h， 生成 N-[3,5-双（三氟甲基）苯基]-N''-[（1R，2R）-2-（1,3-二氢-2H-异吲哚-2-基）环己基]硫脲
  参考文献：
  名称：

  Catalytic Enantioselective Iodoaminocyclization of Hydrazones

  摘要：

  The first catalytic enantioselective iodoaminocyclization of beta,gamma-unsaturated hydrazones has been developed with the help of a trans-1,2-diaminocyclohexane-derived bifunctional thiourea catalyst and allows for the direct access to Delta(2)-pyrazolines containing a quaternary stereogenic center in high yield with good enantioselectivity (up to 95% yield and 95:5 er).

  DOI：

  10.1021/ol5013982
• 作为试剂：
  描述：

  β-硝基苯乙烯 、 1-isobutyl-3-(phenylamino)-1H-pyrrole-2,5-dione 在 N-[3,5-双（三氟甲基）苯基]-N''-[（1R，2R）-2-（1,3-二氢-2H-异吲哚-2-基）环己基]硫脲 作用下， 以 甲苯 为溶剂， 以85 %的产率得到1-isobutyl-3-(2-nitro-1-phenylethyl)-4-(phenylamino)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Takemoto 催化剂催化氨基马来酰亚胺与硝基烯烃的有机催化对映选择性迈克尔反应

  摘要：

  马来酰亚胺被称为亲电子试剂，通常用作迈克尔加成中的受体以生产琥珀酰亚胺。然而，很少进行以马来酰亚胺作为亲核试剂进行对映选择性功能化的反应。在本文中，一系列双功能 Takemoto 催化剂用于有机催化氨基马来酰亚胺与硝基烯烃的对映选择性迈克尔反应。所得产物的收率良好 (76–86%)，对映体过量 (ee) 高达 94%。使用这种方法拓宽了催化剂类型和底物范围。

  DOI：

  10.3390/molecules27227787

文献信息

• Enantioselective Michael Reaction of Malonates to Nitroolefins Catalyzed by Bifunctional Organocatalysts
  作者：Tomotaka Okino、Yasutaka Hoashi、Yoshiji Takemoto

  DOI：10.1021/ja036972z

  日期：2003.10.1

  Michael reaction of malonates to nitroolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities (up to 95%, up to 93% ee).

  丙二酸酯与带有硫脲和叔氨基的手性双功能有机催化剂的迈克尔反应得到了具有高产率和对映选择性（高达 95%，高达 93% ee）的迈克尔加合物。
• [EN] PROCESS AND INTERMEDIATES FOR THE PREPARATION OF NEP INHIBITORS<br/>[FR] PROCESSUS ET INTERMÉDIAIRES POUR LA PRÉPARATION D'INHIBITEURS DE LA NÉPRILYSINE (NEP)
  申请人：NOVARTIS AG

  公开号：WO2016128924A1

  公开（公告）日：2016-08-18

  The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.

  本发明涉及一种新的化学合成方法，中间体和催化剂，用于制备酰肽酶（NEP）抑制剂萨库布曲普。它还涉及新的中间体化合物及其在该新化学合成路线中的使用。
• Asymmetric urea compound and process for producing asymmetric compound by asymmetric conjugate addition reaction with the same as catalyst
  申请人：Takemoto Yoshiji

  公开号：US20060161006A1

  公开（公告）日：2006-07-20

  The present invention relates to a production method of asymmetric compound (IV) which includes conjugately adding nucleophilic reagent (III) to compound (II) in the presence of asymmetric urea compound (I). The present invention provides a non-metallic asymmetric catalyst capable of realizing a highly stereoselective asymmetric conjugate addition reaction in a high yield, and an advantageous production method of an asymmetric compound by an asymmetric conjugate addition reaction using the asymmetric catalyst. wherein X is an oxygen atom or a sulfur atom; C*, C** and C*** are asymmetric carbons; R 1 , R 2 , R 4 , R 5 , R 8 , R 9 and R 10 are each a lower alkyl group optionally having substituent(s) and the like, or R 4 and R 5 and the like in combination optionally form a homocyclic ring optionally having substituent(s) and the like; R 3 is an aryl group optionally having substituent(s) and the like; R 6 and R 7 are each a hydrogen atom and the like; Nu is —CR 16 (COR 17 )(COR 18 ) wherein R 16 , R 17 and R 18 are each a lower alkyl group optionally having substituent(s) and the like, and the like; and EWG is an electron withdrawing group.

  本发明涉及一种不对称化合物（IV）的生产方法，其中在不对称脲化合物（I）的存在下，将亲核试剂（III）共轭加到化合物（II）上。本发明提供了一种非金属不对称催化剂，能够在高产率下实现高度立体选择性的不对称共轭加成反应，并且提供了使用该不对称催化剂进行不对称共轭加成反应的有利生产方法。 其中，X是氧原子或硫原子；C*、C**和C***是不对称碳；R1、R2、R4、R5、R8、R9和R10分别是低级烷基，可选地具有取代基等，或者R4和R5等组合可选地形成具有取代基等的同环烷基；R3是芳基，可选地具有取代基等；R6和R7分别是氢原子等；Nu是—CR16（COR17）（COR18），其中R16、R17和R18分别是低级烷基，可选地具有取代基等；EWG是电子吸引基团。
• ASYMMETRIC UREA COMPOUND AND PROCESS FOR PRODUCING ASYMMETRIC COMPOUND BY ASYMMETRIC CONJUGATE ADDITION REACTION WITH THE SAME AS CATALYST
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP1640361A2

  公开（公告）日：2006-03-29

  The present invention relates to a production method of asymmetric compound (IV) which includes conjugately adding nucleophilic reagent (III) to compound (II) in the presence of asymmetric urea compound (I). The present invention provides a non-metallic asymmetric catalyst capable of realizing a highly stereoselective asymmetric conjugate addition reaction in a high yield, and an advantageous production method of an asymmetric compound by an asymmetric conjugate addition reaction using the asymmetric catalyst. wherein X is an oxygen atom or a sulfur atom; C*, C** and C*** are asymmetric carbons; R1, R2, R4, R5, R8, R9 and R10 are each a lower alkyl group optionally having substituent(s) and the like, or R4 and R5 and the like in combination optionally form a homocyclic ring optionally having substituent(s) and the like; R3 is an aryl group optionally having substituent(s) and the like; R6 and R7 are each a hydrogen atom and the like; Nu is -CR16(COR17) (COR18) wherein R16, R17 and R18 are each a lower alkyl group optionally having substituent(s) and the like, and the like; and EWG is an electron withdrawing group.

  本发明涉及一种不对称化合物（IV）的生产方法，该方法包括在不对称脲化合物（I）存在下将亲核试剂（III）共轭加入到化合物（II）中。本发明提供了一种能够高产率地实现高立体选择性不对称共轭加成反应的非金属不对称催化剂，以及使用该不对称催化剂通过不对称共轭加成反应生产不对称化合物的有利方法。 其中 X 为氧原子或硫原子；C*、C**和 C*** 为不对称碳；R1、R2、R4、R5、R8、R9 和 R10 各为可选具有取代基等的低级烷基，或 R4 和 R5 等组合可选形成可选具有取代基等的均环；R3 是芳基，可选择具有取代基等；R6 和 R7 分别是氢原子等；Nu 是-CR16(COR17) (COR18) 其中 R16、R17 和 R18 分别是低级烷基，可选择具有取代基等；以及 EWG 是析电子基团。
• Process and intermediates for the preparation of NEP inhibitors
  申请人：Novartis AG

  公开号：US10385004B2

  公开（公告）日：2019-08-20

  The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.

  本发明涉及一种新的化学合成方法、中间体和催化剂，可用于制备肾酶（NEP）抑制剂sacubitril。本发明还涉及新的中间体化合物及其在所述新化学合成路线中的用途。