(S)-(-)-1-<4-(2-Methoxyphenyl)-1-piperazinyl>-3-(1-naphthyloxy)-2-propanol | 127931-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-(-)-1-<4-(2-Methoxyphenyl)-1-piperazinyl>-3-(1-naphthyloxy)-2-propanol
• 英文别名: (S)-1-[4-(2-methoxyphenyl)-1-piperazinyl]-3-(1-naphthoxy)-2-propanol；S(-)-naftopidil；(S)-naftopidil；naftopidil；Naftopidil, (S)-；(2S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-naphthalen-1-yloxypropan-2-ol
• CAS: 127931-16-2
• 化学式: C₂₄H₂₈N₂O₃
• 分子量: 392.498
• InChiKey: HRRBJVNMSRJFHQ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-3-(萘-1-氧基)丙烷-1,2-二醇 在 吡啶 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 48.17h， 生成 (S)-(-)-1-<4-(2-Methoxyphenyl)-1-piperazinyl>-3-(1-naphthyloxy)-2-propanol
  参考文献：
  名称：

  Asymmetric Synthesis of Propranolol, Naftopidil and (R)-Monobutyrin using a Glycerol Desymmetrization Strategy

  摘要：

  Herein, an approach for desymmetrization of glycerol by using a readily available camphorsulfonamide as a starting material is described. The strategy for asymmetric synthesis of (R)/(S)-propranolol, (R)/(S)-naftopidil and (R)-monobutyrin with spiroketal formation by desymmetrization was employed and Mitsunobu reaction was used for epoxide and ether formation. Steglich esterification and CAN (cerium ammonium nitrate) mediated ketal deprotection, were key steps in the synthesis. Regioselective ring opening of epoxide gave desired molecule with good overall yield and optical purity.

  DOI：

  10.5935/0103-5053.20130051

文献信息

• The First Enantiomerically Pure Synthesis of (<i>S</i>)- and (<i>R</i>)-Naftopidil Utilizing Hydrolytic Kinetic Resolution of (±)-(α-Naphthyl) Glycidyl Ether
  作者：Kiran Kumar Kothakonda、D. Subhas Bose

  DOI：10.1246/cl.2004.1212

  日期：2004.9

  Hydrolytic Kinetic Resolution (HKR) of (±)-(α-Naphthyl) glycidyl ether with (R,R)-salen Co(III) OAc complex provided enatiomerically pure (S)-naphthyl glycidyl ether and (R)-1-naphthyl glycerol; op...

  (±)-(α-萘基)缩水甘油醚与 (R,R)-salen Co(III) OAc 复合物的水解动力学拆分 (HKR) 提供对映纯的 (S)-萘基缩水甘油醚和 (R)-1-萘基甘油；欧...
• Hydrolytic Kinetic Resolution of α-Naphthyl Glycidyl Ether: A Practical Access to Highly Enantioselective β-Adrenergic Blocking Agents
  作者：D. Subhas Bose、A. V. Reddy、Sanjay W. Chavhan

  DOI：10.1055/s-2005-870021

  日期：——

  Kinetic resolution of (±)-naphthyl glycidyl ether using 0.5 mol% (R,R)-salen Co(III)OAc and water (0.55 equiv) provided enantiomerically pure naphthyl glycidyl ether and 1-naphthylglycerol derivatives with high enantiomeric excess. Application of this approach to highly enantioenriched (S)-naftopidil and (S)-propranolol is described.

  使用0.5摩尔%的(R,R)-salen Co(III)OAc和水（0.55当量）进行的(±)-萘基缩水甘油醚的动力学拆分，获得了高对映体过量率的纯对映体萘基缩水甘油醚和1-萘基甘油衍生物。本文描述了将这种方法应用于高对映体富集的(S)-纳托普地尔和(S)-普萘洛尔的情况。
• Zinc(II) Perchlorate Hexahydrate Catalyzed Opening of Epoxide Ring by Amines:  Applications to Synthesis of (<i>RS</i>)/(<i>R</i>)-Propranolols and (<i>RS</i>)/(<i>R</i>)/(<i>S</i>)-Naftopidils
  作者：Shivani、Brahmam Pujala、Asit K. Chakraborti

  DOI：10.1021/jo062674j

  日期：2007.5.1

  perchlorate hexahydrate was found to be the best catalyst compared to other metal perchlorates. The counteranion modulated the catalytic property of the various Zn(II) compounds that followed the order Zn(ClO4)2·6H2O ≫ Zn(BF4)2 ∼ Zn(OTf)2 ≫ ZnI2 > ZnBr2 > ZnCl2 > Zn(OAc)2 > Zn(CO3)2 in parallelism with the acidic strength of the corresponding protic acids (except for TfOH). The applicability of the methodology

  市售六水合高氯酸锌（II）[Zn（ClO 4）2 ·6H 2已发现O]是一种新型的高效催化剂，用于通过胺在无溶剂条件下以高收率提供2-氨基醇并具有出色的化学，区域和立体选择性的胺来开环。对于不对称环氧化物，区域选择性受与环氧化物和胺相关的电子和空间因素的影响。在氧化苯乙烯与芳族和脂族胺反应过程中观察到区域选择性的互补性：芳族胺是由苯甲基碳的亲核进攻提供的氨基醇，是主要产物，而脂族胺则通过末端碳的反应形成了氨基醇。环氧环的原子是主要/唯一的产物。苯胺与各种缩水甘油醚反应是唯一/主要产物，是在环氧化物的末端碳原子上通过区域选择性亲核攻击而得到的氨基醇。与其他金属高氯酸盐相比，发现六水合高氯酸锌（II）是最好的催化剂。抗衡阴离子按照Zn（ClO）顺序调节了各种Zn（II）化合物的催化性能4）2 ·6H 2 O“的Zn（BF 4）2〜锌（OTF）2 »ZnI 2 > ZnBr 2 >的ZnCl 2
• Conventional Chiralpak ID vs. Capillary Chiralpak ID-3 Amylose Tris-(3-Chlorophenylcarbamate)-Based Chiral Stationary Phase Columns for the Enantioselective HPLC Separation of Pharmaceutical Racemates
  作者：Marwa Ahmed、Marina Gwairgi、Ashraf Ghanem

  DOI：10.1002/chir.22390

  日期：2014.11

  enantioselective analysis using immobilized amylose tris‐(3‐chlorophenylcarbamate) as chiral stationary phase in conventional high‐performance liquid chromatography (HPLC) with Chiralpak ID (4.6 mm ID × 250 mm, 5 µm silica gel) and micro‐HPLC with Chiralpak ID‐3 (0.30 mm ID × 150 mm, 3 µm silica gel) was conducted. Pharmaceutical racemates of 12 pharmacological classes, namely, α‐ and β‐blockers, anti‐inflammatory

  在传统的高效液相色谱（HPLC）中采用Chiralpak ID（4.6 mm ID×250 mm，5 µm硅胶）和Micro-HPLC（Chiralpak），使用固定化直链淀粉三（3-氯苯基氨基甲酸酯）作为手性固定相进行比较对映选择性分析进行ID-3（0.30 mm ID×150 mm，3 µm硅胶）。筛选了12种药理学级别的药物外消旋体，即α和β阻滞剂，抗炎药，抗真菌药，多巴胺拮抗剂，去甲肾上腺素-多巴胺再摄取抑制剂，儿茶酚胺，镇静催眠药，利尿药，抗组胺药，抗癌药和抗心律失常药在正常相位条件下。研究了有机改性剂对分析物保留和对映体识别的影响。对1-ac烯醇，卡洛芬，西脂洛尔，西唑烷醇，咪康唑，戊唑醇，4-羟基-3-甲氧基扁桃酸，1-吲哚醇，1-（2-氯苯基）乙醇，1-苯基-2-丙醇，黄烷酮，6-羟基黄酮，4-溴戊二酰亚胺和戊巴比妥使用常规HPLC，用5 µm硅胶柱填充4.6 mm内径。尽管如此，在装有3
• Investigation into the performance and stability of immobilized and coated polysaccharide columns in supercritical fluid chromatography
  作者：Lei Yue、Madeline Yeh、John Reilly、Bing Wang、Christopher J. Welch、Maria Phan

  DOI：10.1002/chir.23626

  日期：2024.1

  In this study, the performance of the widely used “golden four” coated chiral stationary phases (Chiralpak AD‐3, Chiralcel OD‐3, Chiralpak AS‐3, and Chiralcel OJ‐3) was compared with their corresponding immobilized versions (Chiralpak IA‐3, Chiralpak IB‐3, Chiralpak IB N‐3, Chiralpak IH‐3, and Chiralpak IJ‐3) under supercritical fluid chromatography (SFC) conditions with a set of 30 racemic compounds. Using the traditional modifiers, methanol and isopropanol, the immobilized columns (Chiralpak IB N‐3 and Chiralpak IH‐3) showed an improved general ability to successfully resolve the enantiomers of the target analytes relative to their coated versions (Chiralcel OD‐3 and Chiralpak AS‐3), while the coated columns (Chiralpak AD‐3, Chiralcel OD‐3, and Chiralcel OJ‐3) performed better than their immobilized versions (Chiralpak IA‐3, Chiralpak IB‐3, and Chiralpak IJ‐3). An investigation of the non‐traditional modifiers, dichloromethane, ethyl acetate, and tetrahydrofuran with immobilized columns, revealed a generally decreased ability to successfully resolve the enantiomers of the target analytes, relative to the use of the traditional modifiers, methanol and isopropanol. The stability of the coated columns (Chiralpak AD‐H and Chiralcel OD‐H) was evaluated by injecting “forbidden” solvents, including dichloromethane, dimethyl sulfoxide, and tetrahydrofuran. After 200 injections of these solvents on coated columns, the retention factors and resolutions slightly decreased, and a significant increase in column backpressure was observed, indicating some degree of stationary phase degradation.

  摘要 本研究以一组 30 种外消旋化合物为研究对象，在超临界流体色谱 (SFC) 条件下比较了广泛使用的 "黄金四种 "手性固定相（Chiralpak AD-3、Chiralcel OD-3、Chiralpak AS-3 和 Chiralcel OJ-3）与相应的固定化型手性固定相（Chiralpak IA-3、Chiralpak IB-3、Chiralpak IB N-3、Chiralpak IH-3 和 Chiralpak IJ-3）的性能。使用传统的改性剂甲醇和异丙醇，固定化色谱柱（Chiralpak IB N-3 和 Chiralpak IH-3）在成功分辨目标分析物对映体方面的总体能力优于涂覆型色谱柱（Chiralcel OD-3 和 Chiralpak AS-3）、而涂覆型色谱柱（Chiralpak AD-3、Chiralcel OD-3 和 Chiralcel OJ-3）的性能则优于固定型色谱柱（Chiralpak IA-3、Chiralpak IB-3 和 Chiralpak IJ-3）。对使用固定化色谱柱的非传统修饰剂二氯甲烷、乙酸乙酯和四氢呋喃进行的调查显示，与使用传统修饰剂甲醇和异丙醇相比，成功分辨目标分析物对映体的能力普遍下降。通过注入二氯甲烷、二甲亚砜和四氢呋喃等 "禁用 "溶剂，对涂层柱（Chiralpak AD-H 和 Chiralcel OD-H）的稳定性进行了评估。在涂层色谱柱上注入这些溶剂 200 次后，保留因子和分辨率略有下降，色谱柱背压显著增加，表明固定相发生了一定程度的降解。