4-(4-溴-3-(1,3-二氧戊环-2-基)苯氧基)苯甲腈 | 1217366-74-9

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-溴-3-(1,3-二氧戊环-2-基)苯氧基)苯甲腈
• 英文名称: 4-(4-bromo-3-(1,3-dioxolan-2-yl)phenoxy)benzonitrile
• 英文别名: 4-(4-Bromo-3-(1,3-dioxolan-2-yl)phenoxy)benzonitrile；4-[4-bromo-3-(1,3-dioxolan-2-yl)phenoxy]benzonitrile
• CAS: 1217366-74-9
• 化学式: C₁₆H₁₂BrNO₃
• 分子量: 346.18
• InChiKey: LYBDMDIHPQNASE-UHFFFAOYSA-N

物化性质

• 沸点：
  445.0±45.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

制备方法与用途

该化合物4-［4-溴-3-(1,3-二氧杂环戊烷-2-基)苯氧基］苯甲腈是一种氰化物衍生物，可用作医药中间体。

反应信息

• 作为反应物：
  描述：

  4-(4-溴-3-(1,3-二氧戊环-2-基)苯氧基)苯甲腈 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-(4-溴-3-甲酰基苯氧基)苯甲腈
  参考文献：
  名称：

  Discovery and structure–activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis

  摘要：

  A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.007
• 作为产物：
  描述：

  4-溴-3-(1,3-二氧杂环戊烷-2-基)苯酚 、 对氟苯腈 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(4-溴-3-(1,3-二氧戊环-2-基)苯氧基)苯甲腈
  参考文献：
  名称：

  Discovery and structure–activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis

  摘要：

  A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.007

文献信息

• SOLID STATE FORMS OF CRISABOROLE
  申请人：Pliva Hrvatska d.o.o.

  公开号：US20170305936A1

  公开（公告）日：2017-10-26

  Solid state forms of Crisaborole and salts thereof, processes for preparation thereof and pharmaceutical compositions thereof are disclosed.

  本发明公开了Crisaborole的固态形式及其盐的制备方法和制药组合物。
• 一种克立硼罗中间体的制备方法
  申请人：鲁南制药集团股份有限公司

  公开号：CN113801089A

  公开（公告）日：2021-12-17

  本发明属于药物合成技术领域，具体涉及一种克立硼罗中间体的制备方法。以MED代替现有技术中的乙二醇进行缩醛保护，可显著降低反应温度以及分水器的使用，简化了反应操作，减少能耗。本发明的制备工艺，相较于现有技术所得产品收率及纯度均较高，更适合工业化生产。
• PROCESS FOR THE PREPARATION OF AN INHIBITOR OF PHOSPHODIESTERASE 4
  申请人：Dipharma Francis S.r.l.

  公开号：EP3521293A1

  公开（公告）日：2019-08-07

  The present invention relates to a process for the preparation of Crisaborole in a particular crystalline form 1 as an inhibitor of phosphodiesterase 4, in particular of phosphodiesterase 4B (PDE4B), and intermediates useful for its preparation. The claimed process is characterized by preparing the Crisaborole by hydrolysis of the C1-C5-alkyl ester of formula (X): The crystalline Form 1 is characterized by an XRPD spectrum wherein the most intense peaks, measured using Cu Kα radiation (λ = 1.54 Å), fall at 6.0, 12.1, 14.1, and 15.4 ± 0.2° in 2θ.

  本发明涉及一种作为磷酸二酯酶 4，特别是磷酸二酯酶 4B (PDE4B)抑制剂的 Crisaborole 的特殊结晶形式 1 的制备工艺，以及用于制备该工艺的中间体。所述工艺的特点是通过水解式 (X) 的 C1-C5 烷基酯来制备 Crisaborole： 结晶形式 1 的特征在于 XRPD 光谱，其中使用 Cu Kα 辐射（λ = 1.54 Å）测得的最强光峰位于 2θ 的 6.0、12.1、14.1 和 15.4 ± 0.2°。
• Discovery and structure–activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis
  作者：Tsutomu Akama、Stephen J. Baker、Yong-Kang Zhang、Vincent Hernandez、Huchen Zhou、Virginia Sanders、Yvonne Freund、Richard Kimura、Kirk R. Maples、Jacob J. Plattner

  DOI：10.1016/j.bmcl.2009.03.007

  日期：2009.4

  A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. (C) 2009 Elsevier Ltd. All rights reserved.