2,2-二甲基-3-(甲基氨基)-1-丙醇 | 16047-86-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2,2-二甲基-3-(甲基氨基)-1-丙醇
• 中文别名: 2,2-二甲基-3-(甲基氨基)丙-1-醇
• 英文名称: 2,2-dimethyl-3-(methylamino)propan-1-ol
• CAS: 16047-86-2
• 化学式: C₆H₁₅NO
• mdl: MFCD09864429
• 分子量: 117.191
• InChiKey: ZCCHIQJONBEULF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2922199090

反应信息

• 作为反应物：
  描述：

  2,2-二甲基-3-(甲基氨基)-1-丙醇 在 三乙胺 、 三氯化磷 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以66%的产率得到2-Chloro-3,5,5-trimethyl-1,3,2-oxazaphosphorinane
  参考文献：
  名称：

  Study of the Conformational Equilibria of 2-Z-3-Methyl-1,3,2-oxazaphosphorinanes. Steric and Stereoelectronic Influences on the Orientation of the Me2N Substituent on Three-Coordinate Phosphorus

  摘要：

  The conformations of a series of 1,3,2-oxazaphosphorinanes containing three-coordinate phosphorus, 1-9, have been determined by the use of H-1, P-31, and C-13 NMR spectroscopy. The rings were substituted at ring nitrogen, N(3), with a methyl group to compare its effect on conformational energies with those of 1,3,2-oxazaphosphorinanes reported earlier that featured a larger substituent at N(3), Ph or i-Pr. Quite expectedly, like those rings previously studied with Ph or i-Pr at N(3), a MeO or (CF3)(2)CHO substituent at phosphorus has a strong preference to be axial on a chair-form ring, 1-4, cis-7, and cis-8, or pseudoaxial on a ring in a twist/boat conformation, trans-7. However, when Me(2)N is attached to phosphorus, the newly studied N(3)Me rings display a chair-chair conformational equilibrium, 10 reversible arrow 11, with the Me(2)N equatorial ring, 11, mildly dominant (58/42, 5; 65/35, 6). This contrasts with ratios of 17/83 and 20/80 for the corresponding N(3)Ph analogs, A, and 23/77 for the N(S)-i-Pr compound, B. The observed change in the free energy of the equilibrium 10 reversible arrow 11, 1.2-1.3 kcal/mol, is ascribed to the dominant influence of a decrease in repulsion experienced in conformation 11 between the equatorial Me(2)NP and the smaller Me at N(3)(Me(2)N(eq)/N(3)Me destabilization) compared to that experienced with the N(3)Ph and N(3)-i-Pr analogs. This steric influence of N(3) substituents on the equilibrium 10 reversible arrow 11 is opposite to that found for four-coordinate phosphorus containing 1,3,2-oxazaphosphorinanes in which Me(2)NP(ax/N(3)Ph repulsions that destabilize 10 appear to be dominant.

  DOI：

  10.1021/jo00120a020
• 作为产物：
  描述：

  2,2-二甲基丙二酸单乙酯 在 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 96.0h， 生成 2,2-二甲基-3-(甲基氨基)-1-丙醇
  参考文献：
  名称：

  Study of the Conformational Equilibria of 2-Z-3-Methyl-1,3,2-oxazaphosphorinanes. Steric and Stereoelectronic Influences on the Orientation of the Me2N Substituent on Three-Coordinate Phosphorus

  摘要：

  The conformations of a series of 1,3,2-oxazaphosphorinanes containing three-coordinate phosphorus, 1-9, have been determined by the use of H-1, P-31, and C-13 NMR spectroscopy. The rings were substituted at ring nitrogen, N(3), with a methyl group to compare its effect on conformational energies with those of 1,3,2-oxazaphosphorinanes reported earlier that featured a larger substituent at N(3), Ph or i-Pr. Quite expectedly, like those rings previously studied with Ph or i-Pr at N(3), a MeO or (CF3)(2)CHO substituent at phosphorus has a strong preference to be axial on a chair-form ring, 1-4, cis-7, and cis-8, or pseudoaxial on a ring in a twist/boat conformation, trans-7. However, when Me(2)N is attached to phosphorus, the newly studied N(3)Me rings display a chair-chair conformational equilibrium, 10 reversible arrow 11, with the Me(2)N equatorial ring, 11, mildly dominant (58/42, 5; 65/35, 6). This contrasts with ratios of 17/83 and 20/80 for the corresponding N(3)Ph analogs, A, and 23/77 for the N(S)-i-Pr compound, B. The observed change in the free energy of the equilibrium 10 reversible arrow 11, 1.2-1.3 kcal/mol, is ascribed to the dominant influence of a decrease in repulsion experienced in conformation 11 between the equatorial Me(2)NP and the smaller Me at N(3)(Me(2)N(eq)/N(3)Me destabilization) compared to that experienced with the N(3)Ph and N(3)-i-Pr analogs. This steric influence of N(3) substituents on the equilibrium 10 reversible arrow 11 is opposite to that found for four-coordinate phosphorus containing 1,3,2-oxazaphosphorinanes in which Me(2)NP(ax/N(3)Ph repulsions that destabilize 10 appear to be dominant.

  DOI：

  10.1021/jo00120a020

文献信息

• [EN] DIAZEPINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF HEPATITIS B INFECTIONS<br/>[FR] DÉRIVÉS DE DIAZÉPINONE ET LEUR UTILISATION DANS LE TRAITEMENT DES INFECTIONS PAR L'HÉPATITE B
  申请人：NOVIRA THERAPEUTICS INC

  公开号：WO2018005883A1

  公开（公告）日：2018-01-04

  Provided herein are compounds of formula (I) and (V) useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

  本文提供了一种用于治疗HBV感染的化合物(I)和(V)，以及其药物组合物和抑制、抑制或预防受试者HBV感染的方法。
• [EN] SULFONYLAMINOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS SULFONYLAMINOPYRIDINE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016001341A1

  公开（公告）日：2016-01-07

  Provided are sulfonylaminopyridine compounds that are inhibitors of ITK kinase, compositions containing these compounds and methods for treating diseases mediated by ITK kinase. In particular, provided are compounds of Formula (I), (II) or (III), stereoisomers, tautomers, solvates, prodrugs or pharmaceutically acceptable salts thereof, where n, R1, R2, R3, R6 and R7 are defined herein, pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, for example, for treating a disease or condition mediated by ITK kinase in a patient.

  提供了一种磺酰氨基吡啶化合物，它们是ITK激酶的抑制剂，包含这些化合物的组合物以及治疗由ITK激酶介导的疾病的方法。具体来说，提供了Formula (I)、(II)或(III)的化合物，立体异构体、互变异构体、溶剂合物、前药或其药用可接受的盐，其中n、R1、R2、R3、R6和R7在此处定义，包括含有该化合物和药用可接受的载体、辅料或载体的药物组合物，使用该化合物或组合物进行治疗的方法，例如，用于治疗患有由ITK激酶介导的疾病或病况的患者。
• Identification of potent and selective MTH1 inhibitors
  作者：Alessia Petrocchi、Elisabetta Leo、Naphtali J. Reyna、Matthew M. Hamilton、Xi Shi、Connor A. Parker、Faika Mseeh、Jennifer P. Bardenhagen、Paul Leonard、Jason B. Cross、Sha Huang、Yongying Jiang、Mario Cardozo、Giulio Draetta、Joseph R. Marszalek、Carlo Toniatti、Philip Jones、Richard T. Lewis

  DOI：10.1016/j.bmcl.2016.02.026

  日期：2016.3

  Structure based design of a novel class of aminopyrimidine MTH1 (MutT homolog 1) inhibitors is described. Optimization led to identification of IACS-4759 (compound 5), a sub-nanomolar inhibitor of MTH1 with excellent cell permeability and good metabolic stability in microsomes. This compound robustly inhibited MTH1 activity in cells and proved to be an excellent tool for interrogation of the utility

  描述了基于结构的新型氨基嘧啶MTH1（MutT同系物1）抑制剂的设计。优化导致鉴定IACS-4759（化合物5），MTH1亚纳摩尔抑制剂，在微粒体中具有出色的细胞通透性和良好的代谢稳定性。该化合物强烈抑制细胞中的MTH1活性，并被证明是在肿瘤学背景下研究MTH1抑制作用的极佳工具。
• [EN] NAPHTHYRIDINONE DERIVATIVES AS INHIBITORS OF CYTOMEGALOVIRUS DNA POLYMERASE<br/>[FR] DÉRIVÉS DE NAPHTHYRIDINONE EN TANT QU'INHIBITEURS D'ADN POLYMÉRASE DU CYTOMÉGALOVIRUS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013152063A1

  公开（公告）日：2013-10-10

  Compounds of Formula (I) wherein n, m, R1, R2, R3, R4, R5 and R6 are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.

  式（I）中n、m、R1、R2、R3、R4、R5和R6的化合物，适用于巨细胞病毒疾病和/或感染的治疗。
• Organo-aluminium and -gallium complexes with ω-NH-functional alkoxide ligands
  作者：Alexander Willner、Alexander Hepp、Norbert W. Mitzel

  DOI：10.1039/b811792f

  日期：——

  The aminoalcohols MeNH(CH2)2OH (1), tBuNH(CH2)2OH (2), MeNH(CH2)3OH (3), tBuNH(CH2)3OH (4) and MeNHCH2CMe2CH2OAlMe2 (5) have been reacted with AlMe3 to give the five corresponding aminoalkoxides of the general formula RNH–X–AlMe21a–5a (X = organic spacer between N and O). tBuNHCH2CMe2CH2OH (6) reacts with AlMe3 to give [tBuNHCH2CMe2CH2OAlMe2]·AlMe3 (6a·AlMe3). Analogous reactions of the aminoalcohols 1, 2, 3 and 4 with AltBu3, GaMe3 and GatBu3 afforded the corresponding aminoalkoxides of the general formula RNH–X–MR′21b–4b (MR′2 = AltBu2), 1c–4c (MR′2 = GaMe2) and 1d–4d (MR′2 = GatBu2). The compounds were characterised by NMR spectroscopy, elemental analyses and mass spectrometry. Crystal structures were determined for 3a, 5a, 6a·AlMe3, 3c, 3d, 2d and 4d. Compounds 3a and 5a dimerise via Al2O2 rings, while the amino-functions form intramolecular Al–N bonds. Compounds 3c and 3d form monomers with intramolecular Ga–N bonds. Compounds 2d and 4d are dimers via Ga2O2 rings but in contrast to 3a and 5a without formation of intramolecular Ga–N bonds. 6a·AlMe3 also forms a monomeric compound with intramolecular AlN bond and a further AlMe3 unit bonded to the O atom. The dynamic behaviour of 1d and 2d was investigated by variable-temperature NMR spectroscopy. Some compounds have different aggregation in solid and fluid phases.

  氨基醇MeNH(CH2)2OH (1)、tBuNH( )2OH (2)、MeNH( )3OH (3)、tBuNH( )3OH (4)和MeNH CMe2 OAlMe2 (5)与AlMe3反应，生成了五种通式为RNH－X－AlMe2的相应氨基烷氧化物1a－5a（X = N和O之间的有机间隔基）。tBuNH CMe2 OH (6)与AlMe3反应生成了[tBuNH CMe2 OAlMe2]·AlMe3 (6a·AlMe3)。氨基醇1、2、3和4与AltBu3、GaMe3和GatBu3的类似反应生成了相应通式为RNH－X－MR′2的氨基烷氧化物1b－4b（MR′2 = AltBu2）、1c－4c（MR′2 = GaMe2）和1d－4d（MR′2 = GatBu2）。化合物通过NMR光谱、元素分析和质谱进行了表征。对3a、5a、6a·AlMe3、3c、3d、2d和4d的晶体结构进行了测定。化合物3a和5a通过Al2O2环二聚化，氨基官能团形成分子内Al－N键。化合物3c和3d形成具有分子内Ga－N键的单体。化合物2d和4d通过Ga2O2环二聚化，但与3a和5a不同，不形成分子内Ga－N键。6a·AlMe3也形成具有分子内AlN键的单体化合物，并且还有一个与O原子结合的AlMe3单元。通过变温NMR光谱研究了1d和2d的动力学行为。一些化合物在固体和流体相中具有不同的聚集态。