1-(4-氟苯基)-4-[4-(5-氟嘧啶-2-基)哌嗪-1-基]丁烷-1-酮 | 133982-66-8

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-氟苯基)-4-[4-(5-氟嘧啶-2-基)哌嗪-1-基]丁烷-1-酮
• 英文名称: 1-(4-fluorophenyl)-4-[5-(fluoro-2-pyrimidinyl)-1-piperazinyl]butanone
• 英文别名: 1-(4-fluorophenyl)-4-(4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl)-1-butanone；4'-fluoro-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butyrophenone；1-(4-Fluorophenyl)-4-(4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl)butan-1-one；1-(4-fluorophenyl)-4-[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]butan-1-one
• CAS: 133982-66-8
• 化学式: C₁₈H₂₀F₂N₄O
• 分子量: 346.38
• InChiKey: SFCGNFIBDYIEJN-UHFFFAOYSA-N

物化性质

• 沸点：
  518.9±60.0 °C(Predicted)
• 密度：
  1.247±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-氟苯基)-4-[4-(5-氟嘧啶-2-基)哌嗪-1-基]丁烷-1-酮 生成 alpha-(4-氟苯基)-4-(5-氟-2-嘧啶基)-1-哌嗪丁醇盐酸盐
  参考文献：
  名称：

  J. Nucl. Med. 1993, 34, 246

  摘要：

  DOI：
• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 在 potassium carbonate 、 对甲苯磺酸 、 potassium iodide 作用下， 以 乙腈 、 苯 为溶剂， 反应 54.0h， 生成 1-(4-氟苯基)-4-[4-(5-氟嘧啶-2-基)哌嗪-1-基]丁烷-1-酮
  参考文献：
  名称：

  Synthesis and biological characterization of .alpha.-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogs as potential atypical antipsychotic agents

  摘要：

  A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat. Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects. In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination. The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5-HT1A and alpha1 receptors but was found to be a fairly potent ligand for sigma binding sites (IC50 vs (+)-[H-3]-3-PPP = 112 nM). Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to sigma sites. Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism. The compound has been selected for clinical evaluation in the treatment of psychosis.

  DOI：

  10.1021/jm00102a002

文献信息

• Agents for treatment of brain ischemia
  申请人：Bristol-Myers Squibb Co.

  公开号：US04994460A1

  公开（公告）日：1991-02-19

  A series of 5-halopyrimidin-2-ylpiperazinylalkyl derivatives having useful anti-ischemic properties for treatment and prevention of dirorders resulting from brain and/or spinal cord anoxia.

  一系列具有有用的抗缺血特性的5-卤代嘧啶-2-基哌嗪基烷基衍生物，用于治疗和预防由脑部和/或脊髓缺氧引起的疾病。
• Process for preparing optically active secondary alcohols having nitrogenous or oxygenic functional groups
  申请人：——

  公开号：US20030045727A1

  公开（公告）日：2003-03-06

  A process for preparing optically active secondary alcohols of the general formula (3), [wherein R 1 is linear lower alkyl, an aromatic ring group, or the like; A is CH 2 NR 2 R 3 or the like; n is an integer of 0 to 2; and * represents an asymmetric carbon atom] by asymmetrically hydrogenating a ketone compound of the general formula (1) having nitrogenous or oxygen functional group at any of the a-, &bgr;- and &ggr;-positions, with selectivity among functional groups by the use of a ruthenium/optically active bidentate phosphine/diamine complex as the catalyst in the presence of hydrogen alone or together with a base. The optically active secondary alcohols obtained by the process are useful as drugs and intermediates for the preparation of drugs.

  通过使用钌/光学活性双齿膦/二胺配合物作为催化剂，在存在氢气的情况下或与碱一起，通过不对称地氢化具有氮或氧官能团在α、β和γ位置中的酮化合物（1）来制备通式（3）的光学活性二级醇，[其中R1是线性低碳烷基、芳香环基等；A是CH2NR2R3或类似物；n是0到2的整数；*代表不对称碳原子]。通过该过程获得的光学活性二级醇可用作药物及药物中间体的制备。
• Stereoselective preparation of halophenyl alcohols
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0538693A2

  公开（公告）日：1993-04-28

  A process is described for selectively preparing a compound of the formula wherein: R¹is halogen; R²is halogen, alkyl, cycloalkyl, aryl or and R³is hydrogen, alkyl, cycloalkyl, aryl, or wherein the process comprises treating the associated ketone with an oxido-reductase or a microorganism comprising an oxidoreductase. Compounds prepared by this process are useful antipsychotic agents or useful intermediates therefor.

  描述了一种选择性制备式化合物的工艺 其中 R¹为卤素 R²是卤素、烷基、环烷基、芳基或 和 R³是氢、烷基、环烷基、芳基，或 其中，该工艺包括用氧化还原酶或包含氧化还原酶的微生物处理相关酮。通过该工艺制备的化合物是有用的抗精神病药物或其有用的中间体。
• PROCESS FOR PREPARING OPTICALLY ACTIVE SECONDARY ALCOHOLS HAVING NITROGENOUS OR OXYGENIC FUNCTIONAL GROUPS
  申请人：Asahi Kasei Kabushiki Kaisha

  公开号：EP1254885A1

  公开（公告）日：2002-11-06

  The present invention provides a process for the preparation of an optically active secondary alcohol represented by the general formula (3): wherein R1 represents a straight-chain lower alkyl group, an aromatic ring group, or the like; A represents CH2NR2R3, or the like; n is an integer of from 0 to 2; and * represents an asymmetric carbon atom, which comprises asymmetrically hydrogenating with selectivity among the functional groups, a ketone compound represented by the general formula (1) having a nitrogenous or oxygenic functional group at any of the α-, β- and γ-positions: wherein R1, A and n are as defined above, using a ruthenium/optically active bidentate phosphine/diamine complex as a catalyst in the presence of hydrogen or in the presence of hydrogen and a base. The optically active secondary alcohols obtained by the present process are useful as medicaments and intermediates for producing medicaments.

  本发明提供了一种由通式（3）表示的光学活性仲醇的制备方法： 其中 R1 代表直链低级烷基、芳香环基或类似基团；A 代表 CH2NR2R3 或类似基团；n 是 0 至 2 的整数；以及 * 代表不对称碳原子，其包括以官能团之间的选择性不对称氢化通式 (1) 所代表的酮化合物，该酮化合物在 α-、β- 和 γ- 位置上具有含氮或含氧官能团： 其中 R1、A 和 n 如上定义，使用钌/光学活性双齿膦/二胺络合物作为催化剂，在氢气存在下或在氢气和碱存在下进行。 通过本工艺获得的光学活性仲醇可用作药物和生产药物的中间体。
• Biocatalytic synthesis of some chiral drug intermediates by oxidoreductases
  作者：Ramesh N. Patel、Ronald L. Hanson、Amit Banerjee、Laszlo J. Szarka

  DOI：10.1007/s11746-997-0237-3

  日期：1997.11

  AbstractChiral intermediates were prepared by biocatalytic processes with oxidoreductases for the chemical synthesis of some pharmaceutical drug candidates. These include: (i) the microbial reduction of 1‐(4‐fluorophenyl)‐4‐[4‐(5‐fluoro‐2‐pyrimidinyl)‐1‐piperazinyl]‐1‐butanone (1) to R‐(+)‐1‐(4‐fluorophenyl)‐4‐[4‐(5‐fluoro‐2‐pyrimidinyl)‐1‐piperazinyl]‐1‐butanol (2) [R‐(+)‐BMY 14802], an antipsychotic agent; (ii) the reduction of N‐4‐(1‐oxo‐2‐chloroacetyl ethyl) phenyl methane sulfonamide (3) to the corresponding chiral alcohol (4), an intermediate for d‐(+)‐N‐4‐1‐hydroxy‐2‐[(‐methylethyl)amino]ethyl}phenyl methanesulfonamide [d‐(+) sotalol], a β‐blocker with class III antiarrhythmic properties; (iii) biotransformation of Nɛ‐carbobenzoxy (CBZ)‐l‐lysine (7) to Nɛ‐CBZ‐l‐oxylysine (5), an intermediate needed for synthesis of (S)‐1‐[6‐amino‐2‐[hydroxy(4‐phenylbutyl)phosphinyl]oxy}1‐oxohexyl]‐l‐proline (ceronapril), a new angiotensin converting enzyme inhibitor (6) and (iv) enzymatic synthesis of l‐β‐hydroxyvaline (9) from α‐keto‐β‐hydroxyisovalerate (16). l‐β‐Hydroxyvaline (9) is a key chiral intermediate needed for the synthesis of S‐(Z)‐[1‐(2‐amino‐4‐thiazolyl)‐2‐[2,2‐dimethyl‐4‐oxo‐1‐(sulfooxy)‐3‐azetidinyl] amino}‐2‐oxoethylidene]amino}oxyacetic acid (tigemonam) (10), an orally active monobactam.