4-(4-allyloxymethylfuran-2-yl)-2-chloropyrimidine | 1364123-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(4-allyloxymethylfuran-2-yl)-2-chloropyrimidine
• 英文别名: 2-chloro-4-[4-(prop-2-enoxymethyl)furan-2-yl]pyrimidine
• CAS: 1364123-86-3
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: CZBJSWNVLZMJQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-((烯丙氧基)甲基)-4-(2-(吡咯烷-1-基)乙氧基)苯胺 、 4-(4-allyloxymethylfuran-2-yl)-2-chloropyrimidine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 水 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 17.0h， 生成 15-(2-(pyrrolidin-1-yl)ethoxy)-3,7,12-trioxa-19,21,24-triazatetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2(25),4,9,14(26),15,17,20,22-nonaene
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis

  摘要：

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.

  DOI：

  10.1021/jm201454n
• 作为产物：
  描述：

  4-甲酰基呋喃-2-硼酸 在 甲醇 、 sodium tetrahydroborate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 四丁基硫酸氢铵 、 sodium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 16.0h， 生成 4-(4-allyloxymethylfuran-2-yl)-2-chloropyrimidine
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis

  摘要：

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.

  DOI：

  10.1021/jm201454n

文献信息

• Discovery of the Macrocycle (9<i>E</i>)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis
  作者：Anthony D. William、Angeline C.-H. Lee、Anders Poulsen、Kee Chuan Goh、Babita Madan、Stefan Hart、Evelyn Tan、Haishan Wang、Harish Nagaraj、Dizhong Chen、Chai Ping Lee、Eric T. Sun、Ramesh Jayaraman、Mohammad Khalid Pasha、Kantharaj Ethirajulu、Jeanette M. Wood、Brian W. Dymock

  DOI：10.1021/jm201454n

  日期：2012.3.22

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.