(2-chlorocarboxyethyl)phosphonic acid diethyl ester | 36217-27-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: (2-chlorocarboxyethyl)phosphonic acid diethyl ester
• 英文别名: 3-(Diethoxyphosphoryl)propionyl chloride；3-diethylphosphonopropionyl chloride；3-Diethoxyphosphorylpropanoyl chloride
• CAS: 36217-27-3
• 化学式: C₇H₁₄ClO₄P
• 分子量: 228.613
• InChiKey: BVTYBFVGTRRWGA-UHFFFAOYSA-N

物化性质

• 沸点：
  293.2±23.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-chlorocarboxyethyl)phosphonic acid diethyl ester 在 叠氮基三甲基硅烷 作用下， 以 乙醚 、 甲苯 为溶剂， 生成 [2-(3-Phenyl-ureido)-ethyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  Shokol,V.A. et al., Journal of general chemistry of the USSR, 1974, vol. 44, p. 87 - 89

  摘要：

  DOI：
• 作为产物：
  描述：

  methyl 3-(diethoxyphosphinyl)-propanoate 在 草酰氯 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 (2-chlorocarboxyethyl)phosphonic acid diethyl ester
  参考文献：
  名称：

  A Convenient Horner-Emmons Approach to the Synthesis of Substituted Ethyl 1,3-Butadiene-2-carboxylates, and Related Compounds

  摘要：

  烯丙基膦酸酯3与醛的霍纳-埃蒙斯反应以令人满意的收率得到取代的1,3-丁二烯-2-羧酸酯12。通过对反应物进行适当的改性，可以以高几何选择性制备多种3-烯基-2(5H)呋喃酮13和3-烯基香豆素14。

  DOI：

  10.1055/s-1989-27301

文献信息

• [EN] NOVEL THIOPHENE AMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATING COMPLEMENT-MEDIATED DISEASES AND CONDITIONS<br/>[FR] NOUVELLES AMIDINES DE THIOPHENE, COMPOSITIONS DE CES AMIDINES ET PROCEDE POUR TRAITER DES MALADIES ET DES ETATS MEDIES PAR LE COMPLEMENT
  申请人：DIMENSIONAL PHARM INC

  公开号：WO2003099805A1

  公开（公告）日：2003-12-04

  Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.

  揭示了一种治疗急性或慢性疾病症状的方法，该方法通过补体级联的经典途径介导，包括向需要此类治疗的哺乳动物施用化合物I的治疗有效量或其溶剂化合物、水合物或药用可接受盐；其中规范中定义了R1、R2、R3、R4和R7，Z为SO或SO2，Ar为本规范中定义的芳香族或杂环芳基。
• Diastereoselective Synthesis of Chiral Amidophosphonates by 1,5-Asymmetric Induction
  作者：Géraldine Castelot-Deliencourt、Elisabeth Roger、Xavier Pannecoucke、Jean-Charles Quirion

  DOI：10.1002/1099-0690(200108)2001:16<3031::aid-ejoc3031>3.0.co;2-5

  日期：2001.8

  We have investigated two simple diastereoselective syntheses of substituted β-amidophosphonates. The first one involved a Michael addition to α,β-unsaturated amides 6 and 8a−d, derived from chiral amino alcohols, and permitted the preparation of alkyl-substituted derivatives 7 and 9a−d with high diastereoselectivities (up to 95%) with the aid of a 1,5-asymmetric induction. The second one, involving

  我们研究了取代 β-酰胺基膦酸酯的两种简单的非对映选择性合成。第一个涉及对衍生自手性氨基醇的 α,β-不饱和酰胺 6 和 8a-d 进行迈克尔加成，并允许制备具有高非对映选择性（高达 95%）的烷基取代衍生物 7 和 9a-d 1,5-不对称感应的帮助。第二个涉及手性 β-酰胺基膦酸酯 14a-c 的 1,5-诱导烷基化，在产率方面很有希望，但非对映选择性令人失望（高达 50%）。最后，手性助剂的去除提供了膦酰基羧酸，能够提供对合成生物活性产品非常感兴趣的广泛化合物的途径。
• [EN] TRYPSIN AND THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE TRYPSINE ET DE THROMBINE
  申请人：NOVARTIS AG

  公开号：WO1996029327A1

  公开（公告）日：1996-09-26

  (EN) The present invention provides a compound of general formula (I), in which Ar is a substituted or unsubstituted aryl or heterocyclic residue; Aa is an amino acid residue usually of L configuration and (a) is a residue of formula (IV) or formula (V), wherein X is hydrogen or a C1-C5 alkyl group; Y is a) an SO3H, PO(OR14)2, OH, SH, NR15R16, or halogen group or is b) a residue -(CqH2q)-Q wherein Q is H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 or Hal wherein R14, R15 and R16 are hydrogen, C1-C5 alkyl, C5-C8 cycloalkyl or C7-C11 aralkyl or R15 and R16 together with the nitrogen atom to which they are bound form a 5 or 6 membered azacycloalkyl or oxazacycloalkyl, q is 0 or an integer from 1 to 8 and the residue CqH2q may be optionally substituted by OH or interrupted by oxygen, sulfur, oxycarbonyl O.CO, carbonyloxy CO.O, aminocarbonyl NHCO, sulfonamido, NHSO2 or carboxamido CONH; or is c) a residue (CwH2w+1-y-z)FyOHz in which w is an integer from 1 to 8, y is an integer from 1 to 17 and z is 0 or 1, or X and Y together are = O, Z is a direct bond, oxygen or nitrogen optionally substituted by X or Y, m = 2 to 4, n = 2 to 4 and m + n = 4 to 6, j = 0 to 2, k = 0 to 2 and j + k = 2 or 3, wherein X has its previous significance and Y is a residue (CqH2q)-Q, wherein q and Q have their previous significance, and salts thereof, provided that when As is arginine, X and Y are not alkyl and when Q is COR14, q is an integer from 1 to 8.(FR) La présente invention concerne un composé de la formule générale (I). Dans cette formule, Ar est un reste aryle ou hétérocyclique, substitué ou non; Aa est un reste d'acide aminé ayant généralement la configuration L et (a) est un reste ayant la formule (IV) ou (V). Dans ces formules, X est un hydrogène ou un groupe alkyle C1-C5, Y est a) un SO3H, PO(OR14)2, OH, SH, NR15R16 ou un groupe halogène, ou b) un reste -(CqH2q)-Q où Q est H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 ou Hal où R14, R15 et R16 représentent hydrogène, alkyle C1-C5, cycloalkyle C5-C8 ou aralkyle C7-C11 ou R15 et R16 forment ensemble avec l'atome d'azote auquel ils sont fixés un azacycloalkyle ou un oxazacycloalkyle à 5 - 6 éléments, q est égal à 0 ou à un nombre entier compris entre 1 et 8 et le reste CqH2q peut être, à titre facultatif, substitué par un OH ou interrrompu par un oxygène, un soufre, un oxycarbonyle O.CO, un carbonyloxy CO.O, un aminocarbonyle NHCO, un sulfonamido NHSO2 ou un carboxamido CONH; ou c), un reste (CwH2w+1-y-z)FyOHz dans lequel w est un nombre entier entre 1 et 8, y est un nombre entier entre 1 et 17 et z est égal à 0 ou 1, ou X et Y ensemble = 0, Z est une liaison directe, un oxygène ou un azote substitué éventuellement par X ou Y, m = 2 à 4, et m + n = 4 à 6, j = 0 à 2, k = 0 à 2 et j + k = 2 ou 3, où X a la signification précédente et Y représente un reste (CqH2q)-Q où q et Q ont la signification précédente. L'invention concerne également les sels de ces composés, à condition que, quand Aa représente l'arginine, X et Y ne représentent pas alkyle et quand Q représente COR14, q représente un nombre entier entre 1 et 8.

  本发明提供了一种通式（I）的化合物，其中Ar是取代或未取代的芳基或杂环残基; Aa通常是L构型的氨基酸残基，而（a）是式（IV）或式（V）的残基，其中X是氢或C1-C5烷基基团; Y是a）SO3H、PO（OR14）2、OH、SH、NR15R16或卤素基团，或者b）残基-(CqH2q)-Q，其中Q是H、COR14、CO2R14、CONR15R16、SO3H、OR14、OCOR14、PO（OR14）2、NR15R16、SR14或Hal，其中R14、R15和R16是氢、C1-C5烷基、C5-C8环烷基或C7-C11芳基烷基，或者R15和R16与它们所连接的氮原子形成5或6元杂环烷基或氧杂环烷基，q是0或1-8的整数，而残基CqH2q可以选择性地被OH取代或被氧、硫、氧羰基O.CO、羰氧基CO.O、氨基羰基NHCO、磺酰胺基NHSO2或羧酰胺基CONH打断；或者c）残基（CwH2w+1-y-z）FyOHz，其中w是1-8的整数，y是1-17的整数，z是0或1，或者X和Y一起是=O，Z是直接键，氧或氮，可选地被X或Y取代，m=2-4，n=2-4，m+n=4-6，j=0-2，k=0-2，j+k=2或3，其中X具有其先前的意义，而Y是残基（CqH2q）-Q，其中q和Q具有其先前的意义，以及其盐，但当Aa为精氨酸时，X和Y不是烷基，而当Q为COR14时，q是1-8的整数。
• Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency
  作者：Derek Brundish、Alice Bull、Vera Donovan、Joseph D. Fullerton、Sheila M. Garman、Judy F. Hayler、Diana Janus、Peter D. Kane、Mark McDonnell、Garrick P. Smith、Robert Wakeford、Clive V. Walker、Graham Howarth、William Hoyle、Mark C. Allen、John Ambler、Keith Butler、Mark D. Talbot

  DOI：10.1021/jm9811209

  日期：1999.11.1

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.
• Enantioselective synthesis of (S)-2-amino-3-phosphonopropionic acid, (S)-AP-3, and (R)-2-amino-4-phosphonobutanoic acid, (R)-AP-4, via diastereoselective azidation of (4R,5R)-trans-N-[(diethoxyphosphoryl)propionyl]- and (4R,5R)-trans-N-[(diethoxyphosphoryl)butanoyl]hexahydrobenzoxazolidin-2-one
  作者：Gloria Reyes-Rangel、Virginia Marañón、C. Gabriela Avila-Ortiz、Cecilia Anaya de Parrodi、Leticia Quintero、Eusebio Juaristi

  DOI：10.1016/j.tet.2006.06.018

  日期：2006.8

  N-Acylation of readily available, enantiopure oxazolidinone (4R,5R)-1b with (diethoxyphosphoryl)propionyl chloride and (diethoxyphosphoryl)butanoyl chloride affords de title substrates (4R,5R)-2 and (4R,5R)-7, respectively, which are azidated with high diastereoselectivity by means of the reaction between their sodium enolates (4R,5R)-2-Na and (4R,5R)-7-Na with trisyl azide. Removal of the chiral auxiliary from azidated products (4R,5R,2'S)-3 and (4R,5R,2'R)-8 followed by hydrogenation and hydrolysis of the resulting carboxylic acids (S)-4 and (R)-9 gave the pharmacologically relevant aminophosphonic acids (S)-AP-3 and (R)-AP-4 in good yield. (c) 2006 Elsevier Ltd. All rights reserved.