(S)-4-氰基-5-甲基-4-苯基己醛 | 186763-30-4

• 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: (S)-4-氰基-5-甲基-4-苯基己醛
• 英文名称: (S)-4-cyano-5-methyl-4-phenylhexanal
• 英文别名: (S)-2-isopropyl-5-oxo-2-phenylpentanenitrile；(2S)-5-oxo-2-phenyl-2-propan-2-ylpentanenitrile
• CAS: 186763-30-4
• 化学式: C₁₄H₁₇NO
• 分子量: 215.295
• InChiKey: OAXSBPRAPYEPGP-AWEZNQCLSA-N

物化性质

• 沸点：
  350.2±35.0 °C(Predicted)
• 密度：
  1.009±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-4-氰基-5-甲基-4-苯基己醛 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile
  参考文献：
  名称：

  Enantioselective synthesis of (2S)-5-{4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl}-2-isopropyl-2-phenyl-pentanenitrile dihydrochloride (E2050) using enzyme-catalyzed kinetic resolution

  摘要：

  Immobilized lipase (Pseudomonas sp.)-catalyzed transesterification of (RS)-4-cyano-4-isopropyl-4-phenyl-1-butanol 4 in vinyl acetate gave (S)-4-cyano-4-isopropyl-4-phenyl-1-butyl acetate 3a with high enantiomeric excess values and conversions (95-97% ee, 30-47%, E = 90-93), leaving the enantiomerically pure (R)-alcohol 4 (>99% ee) unreacted. As 3a can be efficiently converted to E2050, use of the immobilized lipase should provide an economical route for large-scale synthesis of E2050. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00364-6
• 作为产物：
  描述：

  (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-4-氰基-5-甲基-4-苯基己醛
  参考文献：
  名称：

  Practical Synthesis of Chiral Emopamil Left Hand as a Bioactive Motif

  摘要：

  An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.

  DOI：

  10.1021/jo020166d

文献信息

• Novel N-substituted alpha aminoacid amides as calcium channel modulators
  申请人：LILLY INDUSTRIES LIMITED

  公开号：EP0805147A1

  公开（公告）日：1997-11-05

  The compounds of formula I and derivatives thereof have been found to be active in tests that show modulation of voltage-dependent calcium channels, and are thus indicated for use in the treatment of diseases in which such modulation is beneficial, in particular diseases of the central nervous system.

  公式I及其衍生物的化合物已被发现在显示调节电压依赖性钙通道的测试中具有活性，因此适用于治疗对此类调节有益的疾病，特别是中枢神经系统疾病。
• Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles
  作者：Long Chen、Maoping Pu、Shiyang Li、Xinpeng Sang、Xiaohua Liu、Yun-Dong Wu、Xiaoming Feng

  DOI：10.1021/jacs.1c08382

  日期：2021.11.17

  centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N′-dioxide–Co(II) complex. The protocol is highly efficient for the construction of nitrile-

  季碳中心的对映选择性构建是不对称催化研究中的一个显着挑战。当手性催化剂不能通过键相互作用区分底物的表面选择性时，这是非常困难的。在这里，我们使用手性N,N'-二氧化物-Co(II)配合物实现了甲硅烷基乙烯酮亚胺与 1-丙烯酰基吡唑的对映选择性迈克尔反应。该协议对于构建含腈、芳基和二烷基的碳中心非常有效，并已成功应用于药物和天然产物的不同合成。未结合的甲硅烷基乙烯酮亚胺和 1-丙烯酰基吡唑键合的催化剂之间的空间分散相互作用在促进该过程的反应性和对映选择性方面起着关键作用。
• Convenient synthesis of (2R)- and (2S)-2-(1-methylethyl)-5-oxo-2-phenylpentanenitrile, intermediates in the preparation of phenylalkylamine calcium channel blockers
  作者：Jeremy Gilmore、Will Prowse、David Steggles、Michael Urquhart、Jennifer Olkowski

  DOI：10.1039/p19960002845

  日期：——

  The multigram synthesis of (2S)- and (2R)-2-(1-methylethyl)-5-oxo-2-phenylpentanenitriles 9a and 9b is described, using either (4R)-2,2-dimethyl-1,3-dioxolan-4-ylmethanol or (2R)-butane-1,2,4-triol as chiral auxiliary. The configuration of an intermediate dioxolane 10b is assigned by X-ray crystallography. The synthetic utility of the aldehydes is demonstrated by conversion to both enantiomers of the

  描述了使用（4 R）-2,2-二甲基-1中的（2 S）-和（2 R）-2-（1-甲基乙基）-5-氧代-2-苯基戊腈9g和9b的多谱合成法1,3-二氧戊环-4-基甲醇或（2 - [R ）-丁烷-1,2,4-三醇作为手性助剂。中间二氧戊环10b的构型通过X射线晶体学确定。醛的合成效用通过> 98％对映体过量（ee）转化为钙拮抗剂去甲环磷酰胺的两种对映体来证明。在手性溶剂化剂（1 R）-（-）-2,2,2-三氟-1-（9-蒽基）乙醇存在下，通过1 H NMR光谱分析最终胺的对映体纯度。
• N-substituted alpha aminoacid amides as calcium channel modulators
  申请人：ELI LILLY AND COMPANY LIMITED

  公开号：EP1041064A2

  公开（公告）日：2000-10-04

  A pharmaceutical compound having the formula in which R1 is alkyl, -SO2R14 where R14 is alkyl, optionally substituted aryl or optionally substituted heteroaryl, R2 is hydrogen, alkyl optionally substituted with one or more hydroxy or C1-4 alkoxy groups, optionally substituted aryl, optionally substituted heteroaryl, -OR15, -P(O)(OR15)(OR16) or -NR15R16 where R15 and R16 are each hydrogen or alkyl, or -SO2R17 where R17 is hydrogen, alkyl, optionally substituted aryl or optionally substituted heteroaryl, R3 is hydrogen, -CN, -CO2R18, -CONR18R19,-CH18≡CHR19, -C≡CR18, -OCH2CO.R18, -SO2R18, -CH2OR18, -CH2OCO.R18, -CH2NHCOR18, -CH2N(COR18)2, -CHO, -OR18, -CH2NR18R19, -CH2OR18, -CH=NR18 or -CH=N-OR18, where R18 and R19 are each hydrogen or alkyl, X is a bond or -SO2-, R4, R5, R6, R8, R9 and R10 are each hydrogen or alkyl, n is 1 to 4, A is -CH2- or -YCO- where Y is a bond, -O-, optionally substituted phenylene, -CH=CH-, or -NR20- where R20 is hydrogen or alkyl, R7 is the C-α substituent of an amino acid or an ester thereof, or R6 and R7 together form a C3-5 alkylene chain optionally substituted by C1-4 alkyl or hydroxyl, or a group of the formula -CH2-Z-CH2- where Z is -CO-, -S-, -SO- or -SO2-, or R7 and R8 together form a C3 to C5 alkylene chain optionally substituted by C1-4 alkyl or hydroxyl, B is -CON(R21)-, -CON(R21)N(R22)- or where -x=y- is -C(R22)=N-, -N=C(R22)- or -N=N-, where R21 is hydrogen, alkyl or -NR23R24 where R23 and R24 are each hydrogen or alkyl, and where R22 is hydrogen or alkyl, or R8 and R21 together form a C2-4 alkylene chain, m is 0 to 2, R11 is hydrogen or alkyl, R12 is hydrogen, alkyl, optionally substituted aryl, optionally substituted heteroaryl, -CN, -OH, -CO2R25, -CONR25R26, where R25 and R26 are each hydrogen or alkyl, and R13 is alkyl, optionally substituted aryl or optionally substituted heteroaryl, or R12 and R13 together form a C3-8 cycloalkyl group or C3-8 cycloalkyl fused to optionally substituted phenyl; or a salt or ester thereof.

  一种药物化合物，其化学式为 其中 R1是烷基、-SO2R14，其中R14是烷基、任选取代的芳基或任选取代的杂芳基、 R2 是氢、任选被一个或多个羟基或 C1-4 烷氧基取代的烷基、任选被取代的芳基、任选被取代的杂芳基、-OR15、 -P(O)(OR15)(OR16)或-NR15R16（其中 R15 和 R16 各为氢或烷基），或-SO2R17（其中 R17 为氢、烷基、任选取代的芳基或任选取代的杂芳基）、 R3 是氢、-CN、-CO2R18、-CONR18R19、-CH18≡CHR19、-C≡CR18、-OCH2CO.R18、-SO2R18、-CH2OR18、-CH2OCO.R18、-CH2NHCOR18、-CH2N(COR18)2、-CHO、-OR18、-CH2NR18R19、-CH2OR18、-CH=NR18 或 -CH=N-OR18，其中 R18 和 R19 各为氢或烷基、 X 是键或-SO2-、 R4、R5、R6、R8、R9 和 R10 各为氢或烷基、 n 为 1 至 4、 A 是-CH2-或-YCO-，其中 Y 是键、-O-、任选取代的亚苯基、-CH=CH-或-NR20-，其中 R20 是氢或烷基、 R7 是氨基酸或其酯的 C-α 取代基，或 R6 和 R7 共同形成任选被 C1-4 烷基或羟基取代的 C3-5 亚烷基链，或式 -CH2-Z-CH2- 的基团，其中 Z 是 -CO-、-S-、-SO- 或 -SO2-、 或 R7 和 R8 共同形成任选被 C1-4 烷基或羟基取代的 C3 至 C5 亚烷基链、 B 是-CON(R21)-、-CON(R21)N(R22)-或 其中-x=y-是-C(R22)=N-、 -N=C(R22)-或-N=N-，其中 R21 是氢、烷基或-NR23R24，其中 R23 和 R24 分别是氢或烷基，R22 是氢或烷基，或 R8 和 R21 共同形成 C2-4 亚烷基链、 m 为 0 至 2、 R11 是氢或烷基 R12 是氢、烷基、任选取代的芳基、任选取代的杂芳基、-CN、-OH、-CO2R25、-CONR25R26，其中 R25 和 R26 各自是氢或烷基，以及 R13 是烷基、任选取代的芳基或任选取代的杂芳基，或 R12 和 R13 共同形成 C3-8 环烷基或与任选取代的苯基融合的 C3-8 环烷基； 或其盐或酯。
• Practical Synthesis of Chiral Emopamil Left Hand as a Bioactive Motif
  作者：Teiji Kimura、Noboru Yamamoto、Yuichi Suzuki、Koki Kawano、Yoshihiko Norimine、Koichi Ito、Satoshi Nagato、Yoichi Iimura、Masahiro Yonaga

  DOI：10.1021/jo020166d

  日期：2002.8.1

  An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.