[1'(R)-α-methylbenzyl]aziridine-2(R)-carboxylate (-)-menthol ester | 397849-98-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [1'(R)-α-methylbenzyl]aziridine-2(R)-carboxylate (-)-menthol ester
• 英文别名: N-[(R)-(+)-α-methylbenzyl]-2(R)-carboxylic acid (-)-menthol ester；N-(R)-α-methylbenzylaziridine-2(R)-carboxylic acid menthyl ester；(-)-menthyl (2R,1'R)-(1'-phenylethyl)aziridine-2-carboxylate；(-)-Menthyl (R)-1-[(R)-alpha-methylbenzyl]aziridine-2-carboxylate；[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] (2R)-1-[(1R)-1-phenylethyl]aziridine-2-carboxylate
• CAS: 397849-98-8
• 化学式: C₂₁H₃₁NO₂
• 分子量: 329.483
• InChiKey: BLLGOPLLCDRJQD-NIPOPRQDSA-N

物化性质

• 熔点：
  75-79°C (lit.)
• 沸点：
  398.7±35.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1'(R)-α-methylbenzyl]aziridine-2(R)-carboxylate (-)-menthol ester 在 silver(I) acetate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 (6R,1'R)-6-(-)-menthylcarbonyl-4-(1'-phenylethyl)morpholine-2,3-dione
  参考文献：
  名称：

  Ring opening of 2-acylaziridines by acid chlorides

  摘要：

  Good nucleophilicity of the ring nitrogen in chiral (2R,1'R)-2-acyl-(1'-phenylethyl)aziridines initiated the reaction with various acid chlorides to form the corresponding acylaziridinium ion intermediates whose rings were opened by the chloride anion to yield the beta-amino-alpha-chlorocarbonyl compounds. The subsequent displacement of the chloride with the internal oxygen nucleophile originated from methylchloroformate, acetyl chloride, and methyl chlorooxoacetate yielded oxazolidin-2-ones, beta-amino-alpha-acetyloxypropionates, and morpholin-2,3-diones, respectively. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.06.025

文献信息

• Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate
  作者：Hyun-Joon Ha、Hyeonsu Jeong、Nagendra Yadav

  DOI：10.1055/s-0036-1588093

  日期：——

  single purification by recrystallization is required after all the chemical transformations, providing the final drug in >99.9% ee. An efficient and scalable synthesis of the antiepileptic drug (R)-lacosamide and its derivatives has been achieved from commercially available aziridine-(2R)-carboxylate in three simple sequential steps, including regioselective aziridine ring opening, debenzylation followed

  摘要 在三个简单的连续步骤中，从市售的氮丙啶-（2 R）-羧酸酯类化合物中，选择性地合成了抗癫痫药（R）-乳糖酰胺及其衍生物，包括区域选择性氮丙啶环开环，脱苄基作用，然后在一个罐中进行乙酰化和酰胺的形成。该方案的优点是起始原料和试剂是可商购的，并且在所有化学转化后都需要通过重结晶进行一次纯化，从而最终药物的ee> 99.9％。 在三个简单的连续步骤中，从市售的氮丙啶-（2 R）-羧酸酯类化合物中，选择性地合成了抗癫痫药（R）-乳糖酰胺及其衍生物，包括区域选择性氮丙啶环开环，脱苄基作用，然后在一个罐中进行乙酰化和酰胺的形成。该方案的优点是起始原料和试剂是可商购的，并且在所有化学转化后都需要通过重结晶进行一次纯化，从而最终药物的ee> 99.9％。
• Preparation of 2,3-diaminopropionate from ring opening of aziridine-2-carboxylate
  作者：Yongeun Kim、Hyun-Joon Ha、Kyusung Han、Seung Whan Ko、Hoseop Yun、Hyo Jae Yoon、Min Sung Kim、Won Koo Lee

  DOI：10.1016/j.tetlet.2005.04.039

  日期：2005.6

  Ring opening reaction of an enantiomerically pure aziridine-2-carboxylate with an azide nucleophile under aqueous acidic media proceeded efficiently and stereoselectively to give 3-amino-2-azidopropionate which is converted to orthogonally protected 2,3-diaminopropionate.

  对映体纯的氮丙啶-2-羧酸盐与叠氮化物亲核试剂在水性酸性介质下的开环反应有效且立体选择性地进行，得到3-氨基-2-叠氮丙酸酯，其转化为正交保护的2，3-二氨基丙酸酯。
• Lewis acid-catalyzed stereospecific ring expansion of aziridine-2-carboxylates to imidazolidin-2-ones
  作者：Min Sung Kim、Yong-Woo Kim、Heung Sik Hahm、Jae Won Jang、Won Koo Lee、Hyun-Joon Ha

  DOI：10.1039/b503750f

  日期：——

  Lewis acid-catalyzed ring expansion reaction of chiral aziridine-2-carboxylate proceeds regio- and stereospecifically to yield enantiomerically pure 4-functionalized imidazolidin-2-ones in high yields.

  路易斯酸催化的手性氮丙啶-2-羧酸手性环扩环反应在区域和立体上进行，以高收率产生对映体纯的4-官能化的咪唑烷基-2-酮。
• [EN] SUBSTITUTED NAPHTHYRIDINES AND THEIR USE AS SYK KINASE INHIBITORS<br/>[FR] NAPHTYRIDINES SUBSTITUÉES ET LEUR UTILISATION COMME INHIBITEURS DE SYK KINASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011092128A1

  公开（公告）日：2011-08-04

  The invention relates to new substituted naphthyridines of formula (1), as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R1 is selected from among -O-R3 or -NR3R4, R3 is C1-6-alkyl which is substituted by R5 and R6 R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, -C1-6-alkylen-O-C1-3-alkyl, C1-3-haloalkyl, R6 is ring X wherein n is either 0 or 1, and Formula (I) is a either a single or a double bond and wherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, -C1-3-alkyl, -C1-3-haloalkyl, -O-C1-3-alkyl, -C1-3-alkanol and halogen, and wherein R4, R2, R7, R8, R9, R10, R11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds.

  该发明涉及公式（1）的新取代萘啉衍生物，以及其药理学上可接受的盐、对映体、非对映体异构体、立体异构体、水合物或溶剂化合物，其中R1从-O-R3或-NR3R4中选择，R3是C1-6-烷基，其被R5和R6取代，R5从氢、支链或直链C1-6-烷基、C2-6-烯基、-C1-6-烷基-氧-C1-3-烷基、C1-3-卤代烷基中选择，R6是环X，其中n为0或1，公式（I）为单键或双键，其中A、B、D和E分别独立地从CH2、CH、C、N、NH、O或S中选择，环X通过位置A、B、D或E连接到分子上，其中所述环X可以选择性地进一步被一个、两个或三个残基取代，每个残基分别从-氧化物、羟基、-C1-3-烷基、-C1-3-卤代烷基、-O-C1-3-烷基、-C1-3-醇基和卤素组成的群中选择，R4、R2、R7、R8、R9、R10、R11和Q的含义可以如权利要求1中所述，以及含有这些化合物的药物组合物。
• SUBSTITUTED NAPHTHYRIDINES AND THEIR USE AS MEDICAMENTS
  申请人：Hoffmann Matthias

  公开号：US20120028939A1

  公开（公告）日：2012-02-02

  The invention relates to new substituted naphthyridines of formula 1, as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R 1 is selected from among —O—R 3 or —NR 3 R 4 , R 3 is C 1-6 -alkyl which is substituted by R 5 and R 6 , R 5 is selected from hydrogen, branched or linear C 1-6 -alkyl, C 2-6 -alkenyl, —C 1-6 -alkylen-O—C 1-3 -alkyl, C 1-3 -haloalkyl, R 6 is ring X wherein n is either 0 or 1, and is a either a single or a double bond and wherein A, B, D and E are each independently from one another selected from CH 2 , CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, —C 1-3 -alkyl, —C 1-3 -haloalkyl, —O—C 1-3 -alkyl, —C 1-3 -alkanol and halogen, and wherein R 4 , R 2 , R 7 , R 8 , R 9 , R 10 , R 11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds.

  该发明涉及公式1的新取代萘啉类化合物，以及其药理学上可接受的盐、对映体、旋光异构体、消旋体、水合物或溶剂合物，其中R1从—O—R3或—NR3R4中选择，R3是经R5和R6取代的C1-6烷基，R5从氢、支链或直链C1-6烷基、C2-6烯基、—C1-6烷基氧基-C1-3烷基、C1-3卤代烷基中选择，R6是环X，其中n为0或1，为单键或双键，A、B、D和E各自独立地从CH2、CH、C、N、NH、O或S中选择，环X通过位置A、B、D或E连接到分子，所述环X可以选择地进一步由氧代、羟基、—C1-3烷基、—C1-3卤代烷基、—O—C1-3烷基、—C1-3烷醇和卤素中的每个单独选择的一个、两个或三个残基取代，并且R4、R2、R7、R8、R9、R10、R11和Q可以具有如权利要求1中所给出的含义，以及含有这些化合物的药物组合物。