5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile | 1082444-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile
• 英文别名: 5-bromo-2-(2,6-difluorophenyl)-1,3-oxazole-4-carbonitrile
• CAS: 1082444-71-0
• 化学式: C₁₀H₃BrF₂N₂O
• 分子量: 285.047
• InChiKey: YHOUJVMWXYCTEU-UHFFFAOYSA-N

物化性质

• 沸点：
  394.2±52.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile 在 硫酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 4.0h， 以94%的产率得到5-bromo-2-(2,6-difluorophenyl)oxazole-4-carboxamide
  参考文献：
  名称：

  WO2008/139161

  摘要：

  公开号：
• 作为产物：
  描述：

  2,6-二氟苯甲酰氯 在 亚硝酸特丁酯 、 copper(ll) bromide 作用下， 以 N-甲基吡咯烷酮 、 乙腈 为溶剂， 反应 1.08h， 生成 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile
  参考文献：
  名称：

  WO2008/139161

  摘要：

  公开号：

文献信息

• [EN] PHARMACEUTICAL COMPOUNDS<br/>[FR] COMPOSÉS PHARMACEUTIQUES
  申请人：SAREUM LTD

  公开号：WO2015032423A1

  公开（公告）日：2015-03-12

  The invention provides a compound which is an amide of the formula (2): or a salt or stereoisomer thereof; wherein: R7 is selected from chlorine and fluorine; R3, R4, R5 and R6 are each independently selected from hydrogen, fluorine and chlorine; n is 0, 1 or 2; Q1 is selected from C(=O), S(=O) and SO2; A is absent or is NR2; R1 is selected from: - hydrogen; - an optionally substituted C1-6 non-aromatic hydrocarbon group; and - 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms, the carbocyclic and heterocyclic rings and bridged bicyclic heterocyclic rings being optionally substituted; R2 is selected from hydrogen and C1-4 alkyl; or NR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen- containing heterocyclic ring optionally containing a second heteroatom ring member selected from nitrogen and oxygen; with the provisos that: (i) no more than two of R3 to R6 are other than hydrogen; and (ii) when R7 and R6 are both fluorine, then one of R3 to R5 is chlorine or fluorine and/or R1-A-Q1 is selected from ethylsulfonyl and isopropylsulfonyl. Also provided are pharmaceutical compositions containing the compounds and their therapeutic uses.

  本发明提供的化合物是公式（2）的酰胺或其盐或立体异构体；其中：R7从氯和氟中选择；R3、R4、R5和R6各自独立地从氢、氟和氯中选择；n为0、1或2；Q1从C（=O）、S（=O）和SO2中选择；A不存在或为NR2；R1从：-氢；-可选择取代的C1-6非芳香烃基；和-含有一个或两个杂原子环成员（选自O、N和S）的3-至7元非芳香碳环和杂环，并且是由七个至九个环成员的桥接双环杂环，其中一个或两个是氮原子，所述碳环和杂环以及桥接双环杂环可选择取代；R2从氢和C1-4烷基中选择；或NR1R2形成一个可选择取代的4-至7元非芳香含氮杂环，可选择包含第二个杂原子环成员，选自氮和氧；但前提是：（i）R3至R6中不超过两个不是氢；（ii）当R7和R6均为氟时，那么R3至R5中的一个为氯或氟和/或R1-A-Q1选择自乙基磺酰基和异丙基磺酰基。还提供了含有该化合物的药物组合物及其治疗用途。
• Oxazole tyrosine kinase inhibitors
  申请人：Reader John Charles

  公开号：US08378095B2

  公开（公告）日：2013-02-19

  The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Ar1 is a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted by one or more substituents R1; Ar2 Js a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R2; and R1 and R2 are as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases.

  本发明提供了一种化合物，其为公式（1）的酰胺或其盐、溶剂合物、N-氧化物或互变异构体；其中：a为0或1；b为0或1：前提是a和b的和为0或1；T为O或NH；Ar1为单环或双环的5-至10-成员芳基或杂芳基，包含最多4个从O、N和S中选择的杂原子，并且可以被一个或多个取代基R1取代；Ar2为单环或双环的5-至10-成员芳基或杂芳基，包含最多4个从O、N和S中选择的杂原子，并且可以被一个或多个取代基R2取代；其中R1和R2如权利要求所定义。这些化合物是激酶抑制剂，特别是FLT3、FLT4和Aurora激酶的抑制剂。
• OXAZOLE TYROSINE KINASE INHIBITORS
  申请人：Sareum Limited

  公开号：US20130102592A1

  公开（公告）日：2013-04-25

  The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Ar 1 is a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted en by one or more substituents R 1 ; Ar 2 Js a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R 2 ; and R 1 and R 2 are as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases.

  本发明提供了一种化合物，其为公式（1）的酰胺或其盐、溶剂合物、N-氧化物或互变异构体；其中：a为0或1；b为0或1：前提是a和b的和为0或1；T为O或NH；Ar1为含有最多4个来自O、N和S的杂原子的单环或双环5-至10-成员芳基或杂芳基基团，并且可以被一个或多个取代基R1取代；Ar2为含有最多4个来自O、N和S的杂原子的单环或双环5-至10-成员芳基或杂芳基基团，并且可以被一个或多个取代基R2取代；R1和R2如权利要求所定义。该化合物是激酶抑制剂，特别是FLT3、FLT4和Aurora激酶的抑制剂。
• PHARMACEUTICAL COMPOUNDS
  申请人：SAREUM LIMITED

  公开号：US20130231340A1

  公开（公告）日：2013-09-05

  The invention provides a method of inhibiting a TYK2 kinase, which method comprises bringing into contact with the TYK2 kinase an effective TYK2 kinase-inhibiting amount of a compound having the formula (0): or a salt or stereoisomer thereof. The invention also provides a novel subset of compounds within formula (0) as well as pharmaceutical compositions containing them and their use in medicine.

  本发明提供了一种抑制TYK2激酶的方法，该方法包括将具有以下式子（0）的化合物或其盐或立体异构体的有效TYK2激酶抑制剂量与TYK2激酶接触。本发明还提供了公式（0）内的新化合物子集，以及包含它们的药物组合物及其在医学中的应用。
• TYK2 kinase inhibitors
  申请人：Sareum Limited

  公开号：EP2634185A1

  公开（公告）日：2013-09-04

  The invention provides a compound which is an amide of the formula (2): or a salt or stereoisomer thereof; wherein: R7 is selected from chlorine and fluorine; R3, R4, R5 and R6 are each independently selected from hydrogen, fluorine and chlorine; n is 0, 1 or 2; Q1 is selected from C(=O), S(=O) and SO2; A is absent or is NR2; R1 is selected from: - hydrogen; - an optionally substituted C1-6 non-aromatic hydrocarbon group; and - 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms, the carbocyclic and heterocyclic rings and bridged bicyclic heterocyclic rings being optionally substituted; R2 is selected from hydrogen and C1-4 alkyl; or NR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic ring optionally containing a second heteroatom ring member selected from nitrogen and oxygen; with the provisos that: (i) no more than two of R3 to R6 are other than hydrogen; and (ii) when R7 and R6 are both fluorine, then one of R3 to R5 is chlorine or fluorine and/or R1-A-Q1 is selected from ethylsulfonyl and isopropylsulfonyl. Also provided are pharmaceutical compositions containing the compounds and their therapeutic uses.

  本发明提供了一种化合物，它是式 (2) 的酰胺： 或其盐或立体异构体；其中 R7 选自氯和氟； R3、R4、R5 和 R6 各自独立地选自氢、氟和氯； n 是 0、1 或 2； Q1 选自 C（=O）、S（=O）和 SO2； A 不存在或为 NR2； R1 选自 - 氢 - 任选取代的 C1-6 非芳香烃基团；和 - 含有一个或两个选自 O、N 和 S 的杂原子环成员的 3 至 7 元非芳族碳环和杂环，以及由 7 至 9 个环成员（其中一个或两个为氮原子）组成的桥接双环杂环，碳环和杂环以及桥接双环杂环可任选被取代； R2 选自氢和 C1-4 烷基；或 NR1R2 形成任选取代的 4 至 7 元非芳族含氮杂环，该杂环任选含有选自氮和氧的第二个杂原子环成员； 但条件是 (i) R3 至 R6 中不超过两个不是氢；以及 (ii) 当 R7 和 R6 都是氟时，则 R3 至 R5 中的一个是氯或氟，和/或 R1-A-Q1 选自乙基磺酰基和异丙基磺酰基。 此外，还提供了含有这些化合物的药物组合物及其治疗用途。