2-chloro-7-fluoro-1,5-diazanaphthalene | 1378470-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-chloro-7-fluoro-1,5-diazanaphthalene
• 英文别名: 2-chloro-7-fluoro-1,5-naphthyridine；2-Chloro-7-fluoro-1,5-naphthyridine
• CAS: 1378470-92-8
• 化学式: C₈H₄ClFN₂
• 分子量: 182.585
• InChiKey: LCPAJDYXZGMQJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  285.4±35.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-7-fluoro-1,5-diazanaphthalene 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.5h， 生成 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine
  参考文献：
  名称：

  A One-Pot Diazotation–Fluorodediazoniation Reaction and Fluorine Gas for the Production of Fluoronaphthyridines

  摘要：

  Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like Select Fluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5-naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).

  DOI：

  10.1021/op500100b
• 作为产物：
  描述：

  2,6-二氯-5-氟烟酸 在 甲酸 、 三丁基膦 、 叠氮磷酸二苯酯 、 palladium diacetate 、 sodium carbonate 、 溶剂黄146 、 三乙胺 、 三苯基膦 、 叔丁醇 、 三氯氧磷 作用下， 以 乙酸丁酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-chloro-7-fluoro-1,5-diazanaphthalene
  参考文献：
  名称：

  A One-Pot Diazotation–Fluorodediazoniation Reaction and Fluorine Gas for the Production of Fluoronaphthyridines

  摘要：

  Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like Select Fluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5-naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).

  DOI：

  10.1021/op500100b

文献信息

• [EN] BICYCLIC HETEROCYCLE SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS KINASE MODULATORS<br/>[FR] COMPOSÉS PYRIDYLES À SUBSTITUTION PAR HÉTÉROCYCLE BICYCLIQUE UTILES EN TANT QUE MODULATEURS DE KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014074657A1

  公开（公告）日：2014-05-15

  Compounds having the following formula (I) or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein R2 is a bicyclic heterocycle, and R1, R3, R4, R5 and R6 are as defined herein, that are useful as kinase modulators, including IRAK-4 modulation.

  具有以下式(I)的化合物或其立体异构体或药用盐，其中R2是双环杂环，R1、R3、R4、R5和R6如本文所定义，这些化合物可用作激酶调节剂，包括IRAK-4调节。
• Target-Directed Synthesis of Antibacterial Drug Candidate GSK966587
  作者：Eric A. Voight、Hao Yin、Susan V. Downing、Stacie A. Calad、Hayao Matsuhashi、Ilaria Giordano、Alan J. Hennessy、Richard M. Goodman、Jeffery L. Wood

  DOI：10.1021/ol101235f

  日期：2010.8.6

  An efficient enantioselective total synthesis of the potent antibiotic GSK966587 was accomplished. Highlights of the synthesis include two innovative Heck reactions, a highly selective zincate base directed ortho-metalation, Sharpless asymmetric epoxidation, and a fully convergent final step fragment coupling.

  完成了强效抗生素GSK966587的有效对映选择性全合成。合成的亮点包括两个创新的Heck反应，高选择性的锌酸酯基定向原金属化，Sharpless不对称环氧化和完全收敛的最终步骤片段偶联。
• BICYCLIC HETEROCYCLE SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS KINASE MODULATORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150274696A1

  公开（公告）日：2015-10-01

  Compounds having the following formula (I) or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein R 2 is a bicyclic heterocycle, and R 1 , R 3 , R 4 , R 5 and R 6 are as defined herein, that are useful as kinase modulators, including IRAK-4 modulation.

  具有以下式(I)或其立体异构体或药物可接受的盐的化合物，其中R2是双环杂环，R1、R3、R4、R5和R6如此定义，可用作激酶调节剂，包括IRAK-4调节剂。
• US9546153B2
  申请人：——

  公开号：US9546153B2

  公开（公告）日：2017-01-17
• A One-Pot Diazotation–Fluorodediazoniation Reaction and Fluorine Gas for the Production of Fluoronaphthyridines
  作者：Stefan Abele、Gunther Schmidt、Matthew J. Fleming、Heinz Steiner

  DOI：10.1021/op500100b

  日期：2014.8.15

  Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like Select Fluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5-naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).