(R)-(-)-N-(3-pyridylmethylidene)-2-methylpropane-2-sulfinamide | 220315-22-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-(-)-N-(3-pyridylmethylidene)-2-methylpropane-2-sulfinamide
• 英文别名: 3-pyridylmethylene-N-tert-butanesulfinyl imine；(R,E)-2-methyl-N-(pyridin-3-ylmethylene)propane-2-sulfinamide；(R)-2-Methyl-N-(pyridin-3-ylmethylene)-propane-2-sulfinamide；(NE,R)-2-methyl-N-(pyridin-3-ylmethylidene)propane-2-sulfinamide
• CAS: 220315-22-0
• 化学式: C₁₀H₁₄N₂OS
• 分子量: 210.3
• InChiKey: BMQNAHRVOYMEED-CEFACKQISA-N

物化性质

• 沸点：
  359.6±34.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(-)-N-(3-pyridylmethylidene)-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 生成 (alphaS)-alpha-甲基-3-吡啶甲胺
  参考文献：
  名称：

  通过构型稳定的α-吡啶基有机锂的2-和3-吡啶基取代的烷基胺的立体特异性分子内芳​​基化

  摘要：

  用碱处理对映体富集的α-（2-吡啶基）和α-（3-吡啶基）烷基胺的N'-芳基脲衍生物会导致N'-芳基取代基从N迁移至C的“非经典”状态分子内亲核芳族取代反应。富电子环和贫电子环均成功迁移。即使当中间阴离子可能是平面的2-甲基吡啶基锂时，在吡啶环附近也会形成一个新的立体立体中心，该中心具有很高的立体特异性。脲的碱水解得到对映体富集的α-吡啶基烷基胺。

  DOI：

  10.1021/acs.orglett.6b03603
• 作为产物：
  描述：

  3-吡啶甲醛 、 (R)-(+)-叔丁基亚磺酰胺 在 titanium(IV) tetraethanolate 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以82%的产率得到(R)-(-)-N-(3-pyridylmethylidene)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  手性亚磺酰基亚胺的 Corey-Chaykovsky 反应：形成手性氮丙啶的简便方法

  摘要：

  介绍了二甲基锍与一系列芳香族、杂环和脂肪族叔丁基亚磺酰基亚胺的反应。氮丙啶以 63-84% 的产率和 77-95% 的非对映体过量形成。

  DOI：

  10.1055/s-2003-42028

文献信息

• Diastereoselective Cyanomethylation of Chiral<i>N</i>-(<i>tert</i>-Butylsulfinyl)imines Promoted by Lewis Bases
  作者：Teruaki Mukaiyama、Makoto Michida

  DOI：10.1246/cl.2007.1244

  日期：2007.10.5

  Cyanomethylation of chiral N-(tert-butylsulfinyl)imines with 2-trimethylsilylacetonitrile (TMSCH2CN) in the presence of a Lewis base such as tetrabutylammonium phenoxide (PhONn-Bu4) proceeds smoothly to afford the corresponding β-amino nitriles in good to high yields with excellent diastereoselectivities.

  在路易斯碱（如四丁基氧化酚铵（PhONn-Bu4））存在下，用 2-三甲基硅乙腈（TMSCH2CN）对手性 N-(叔丁基亚磺酰基)亚胺进行氰甲基化反应，可以顺利得到相应的 β-氨基腈，产率从好到高，非对映选择性极佳。
• COMPOUND HAVING BET INHIBITORY ACTIVITY AND PREPARATION METHOD AND USE THEREFOR
  申请人：Shanghai Haihe Pharmaceutical Co., Ltd.

  公开号：EP3750885A1

  公开（公告）日：2020-12-16

  The invention relates to the field of pharmaceutical chemistry. Specifically, the present invention relates to a series of BET (bromodomain and extra-terminal domain) inhibitors having a novel structure, particularly inhibitors targeting BRD4 (Bromodomain-containing protein 4), and a preparation method and use therefor. The structure thereof is shown in the following general formula (I). Said compounds or a stereoisomer, racemate, geometric isomer, tautomer, prodrug, hydrate, solvate, or crystal form thereof, or a pharmaceutically acceptable salt thereof, and the pharmaceutical compsosition thereof can be used for the treatment and/or prevention of related diseases mediated by bromodomain proteins.

  本发明涉及药物化学领域。具体地说，本发明涉及一系列具有新型结构的 BET（溴基二甲基和端外域）抑制剂，特别是针对 BRD4（含溴基二甲基蛋白 4）的抑制剂，以及其制备方法和用途。其结构如下通式（I）所示。所述化合物或其立体异构体、外消旋体、几何异构体、同分异构体、原药、水合物、溶液或晶体形式，或其药学上可接受的盐，以及其药物组合物可用于治疗和/或预防由溴基团蛋白介导的相关疾病。
• Synthesis of Enantiomerically Pure <i>N</i>-<i>tert</i>-Butanesulfinyl Imines (<i>tert</i>-Butanesulfinimines) by the Direct Condensation of <i>tert</i>-Butanesulfinamide with Aldehydes and Ketones
  作者：Guangcheng Liu、Derek A. Cogan、Timothy D. Owens、Tony P. Tang、Jonathan A. Ellman

  DOI：10.1021/jo982059i

  日期：1999.2.1

  Experimental details for the first general methods for the one-step preparation of N-tert-butanesulfinyl imines (tert-butanesulfinimines) (2) from aldehydes and ketones is described. To effect the condensations of tert-butanesulfinamide (1) with aldehydes, the Lewis acidic dehydrating agents MgSO4, CuSO4, or Ti(OEt)(4) are employed. Aldehyde condensations mediated by MgSO4 proceed in high yields (84-96%) when an excess of aldehyde is used. In contrast, only a slight excess of aldehyde (1.1 equiv) relative to tert-butanesulfinamide provides sulfinimines in high yields when the more Lewis acidic dehydrating agent CuSO4 is used. The CuSO4-mediated procedure is effective for a wide range of aldehydes, including sterically demanding aldehydes, such as isobutyraldehyde (90%), and electron-rich aldehydes, such as p-anisaldehyde (81%). The still more Lewis acidic Ti(OEt)(4) and Ti(O-i-Pr)(4) also afford N-tert-butanesulfinyl aldimines from especially unreactive aldehydes, such as pivaldehyde (82%). In addition, Ti(OEt)(4) is effective for the condensation of I with ketones to afford a wide range of N-tert-butanesulfinyl ketimines in good yields (77-91%). For sulfinyl ketimines derived from methyl or n-alkyl phenyl ketones and methyl or n-alkyl isopropyl ketones, only the E isomer is detected by H-1 and C-13 NMR in CDCl3. For those cases where the difference in steric demand about the imine is very small, such as for 2-hexanone, high E/Z ratios are still observed (5:1).
• Asymmetric Synthesis of β-Amino Acid Derivatives Incorporating a Broad Range of Substitution Patterns by Enolate Additions to <i>tert</i>-Butanesulfinyl Imines
  作者：Tony P. Tang、Jonathan A. Ellman

  DOI：10.1021/jo025957u

  日期：2002.11.1

  Addition of Ti(Oi-Pr)(3) ester enolates to tert-butanesulfinyl aldimines and ketimines provided beta-substituted, alpha,beta- and beta,beta-disubstituted, alpha,beta,beta- and alpha,alpha,beta-trisubstituted, and alpha,alpha,beta,beta-tetrasubstituted beta-amino acid derivatives in high yields and with high diastereoselectivites. The N-sulfinyl-beta-amino ester products were further employed as versatile intermediates for both standard solution-phase and solid-phase synthetic transformations, including the synthesis of beta-peptide foldamers.
• The <i>tert</i>-Butanesulfinyl Group:  An Ideal Chiral Directing Group and Boc-Surrogate for the Asymmetric Synthesis and Applications of β-Amino Acids
  作者：Tony P. Tang、Jonathan A. Ellman

  DOI：10.1021/jo9820824

  日期：1999.1.1