benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-fluoropyrrolidine-1-carboxylate | 1776114-06-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-fluoropyrrolidine-1-carboxylate
• 英文别名: trans-Benzyl 3-(tert-butoxycarbonylamino)-4-fluoropyrrolidine-1-carboxylate；benzyl (3R,4R)-3-fluoro-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidine-1-carboxylate
• CAS: 1776114-06-7
• 化学式: C₁₇H₂₃FN₂O₄
• 分子量: 338.379
• InChiKey: YQMILGMYFPDLLN-ZIAGYGMSSA-N

物化性质

• 沸点：
  465.5±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-fluoropyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到benzyl (3R,4R)-3-amino-4-fluoropyrrolidine-1-carboxylate
  参考文献：
  名称：

  利用Burgess型转化对映体合成（3 R，4 R）-1-苄基-4-氟吡咯烷-3-胺

  摘要：

  EGFR抑制剂的生产需要不对称合成适合中试规模的关键3,4-反式取代的吡咯烷。最初的合成路线使用的试剂和中间体由于其能量潜力而引起安全隐患，然后需要超临界流体色谱法才能获得所需的单一对映异构体。伯吉斯型试剂在有机合成中具有巨大的实用性，但由于成本高且不稳定，因此在大规模使用中受到限制。然而，广泛的工艺开发导致了规模友好的工艺，其中Boc-Burgess试剂的原位形成使得能够从廉价的材料中获得手性环状氨基磺酸盐。ReactIR监测用于研究中间稳定性，并能够在多千克规模上进行处理。氨基磺酸盐转化为具有完全立体特异性的反式-3-氟-4-氨基吡咯烷1。中等结晶度提供了纯度控制点，可以排除副产物和杂质，从而无需色谱。

  DOI：

  10.1021/acs.oprd.9b00245
• 作为产物：
  描述：

  3-benzyl 6-tert-butyl-3,6-diazabicyclo[3.1.0]hexane-3,6-dicarboxylate 在 六氟异丙醇 、 苯甲酰氟 、 1,5-二氮杂双环[4.3.0]壬-5-烯 作用下， 以 甲基叔丁基醚 为溶剂， 反应 24.0h， 以83%的产率得到benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-fluoropyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of β-Fluoroamines by Lewis Base Catalyzed Hydrofluorination of Aziridines

  摘要：

  Lewis base catalysis promotes the in situ generation of amine-HF reagents from benzoyl fluoride and a non-nucleophilic alcohol. The hydrofluorination of aziridines to provide beta-fluoroamines using this latent HF source is described. This protocol displays a broad scope with respect to aziridine substitution and N-protecting groups. Examples of regio- and diastereoselective ring opening to access medicinally relevant beta-fluoroamine building blocks are presented.

  DOI：

  10.1021/jo300433a

文献信息

• PURINE DERIVATIVES
  申请人：PFIZER INC.

  公开号：US20150141402A1

  公开（公告）日：2015-05-21

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, G, ring A, ring B, R 1 , R 2 , R 3 , R 4 , R 5 , R 5a , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , and m are defined herein. The novel purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

  本发明涉及式(I)的化合物或其药用盐，其中Q、G、环A、环B、R1、R2、R3、R4、R5、R5a、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17、R18、R19、R20、R21、R22、R23、R24和m在此定义。这些新颖的嘌呤衍生物在治疗哺乳动物中的异常细胞生长，如癌症方面具有用途。另外，还涉及含有这些化合物的药物组合物，以及在治疗哺乳动物中的异常细胞生长方面使用这些化合物和组合物的方法。
• [EN] COMPOUNDS AS RAS INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS EN TANT QU'INHIBITEURS DE RAS ET LEURS UTILISATIONS
  申请人：BIOARDIS LLC

  公开号：WO2022087624A1

  公开（公告）日：2022-04-28

  The present disclosure relates generally to compounds and compositions thereof for inhibition of RAS, such as KRAS, HRAS and NRAS, including mutant forms of KRAS, HRAS and NRAS, particularly those harboring a G12C mutation, methods of preparing said compounds and compositions, and their use in the treatment or prophylaxis of various cancers, such as lung cancer, colorectal cancer, pancreatic cancer, gall bladder cancer, thyroid cancer, and bile duct cancer.

  本公开涉及抑制RAS的化合物和其组成物，例如KRAS、HRAS和NRAS，包括带有G12C突变的KRAS、HRAS和NRAS的突变形式，制备这些化合物和组合物的方法，以及它们在治疗或预防各种癌症方面的用途，例如肺癌、结直肠癌、胰腺癌、胆囊癌、甲状腺癌和胆管癌。
• Purine derivatives
  申请人：PFIZER INC.

  公开号：US09290496B2

  公开（公告）日：2016-03-22

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, G, ring A, ring B, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, and m are defined herein. The novel purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

  本发明涉及式(I)的化合物或其药学上可接受的盐，其中Q、G、环A、环B、R1、R2、R3、R4、R5、R5a、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17、R18、R19、R20、R21、R22、R23、R24和m在此定义。这些新型嘌呤衍生物在哺乳动物的异常细胞生长（如癌症）的治疗中有用。另外，本发明还涉及含有这些化合物的制药组合物以及在哺乳动物的异常细胞生长治疗中使用这些化合物和组合物的方法。
• Discovery of <i>N</i>-((3<i>R</i>,4<i>R</i>)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1<i>H</i>-pyrazol-4-yl)amino)-9-methyl-9<i>H</i>-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR
  作者：Simon Planken、Douglas C. Behenna、Sajiv K. Nair、Theodore O. Johnson、Asako Nagata、Chau Almaden、Simon Bailey、T. Eric Ballard、Louise Bernier、Hengmiao Cheng、Sujin Cho-Schultz、Deepak Dalvie、Judith G. Deal、Dac M. Dinh、Martin P. Edwards、Rose Ann Ferre、Ketan S. Gajiwala、Michelle Hemkens、Robert S. Kania、John C. Kath、Jean Matthews、Brion W. Murray、Sherry Niessen、Suvi T. M. Orr、Mason Pairish、Neal W. Sach、Hong Shen、Manli Shi、James Solowiej、Khanh Tran、Elaine Tseng、Paolo Vicini、Yuli Wang、Scott L. Weinrich、Ru Zhou、Michael Zientek、Longqing Liu、Yiqin Luo、Shuibo Xin、Chengyi Zhang、Jennifer Lafontaine

  DOI：10.1021/acs.jmedchem.6b01894

  日期：2017.4.13

  Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants, was recently disclosed.(1) Herein, we describe our continued efforts to achieve potency across EGFR oncogenic mutations and improved kinome selectivity, resulting in the discovery of clinical candidate PF-06747775 (21), which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. Compound 21 is currently being evaluated in phase-I clinical trials of mutant EGFR driven NSCLC.
• Synthesis and structure-activity relationships of 2-pyridones: II. 8-(Fluoro-substituted pyrrolidinyl)-2-pyridones as antibacterial agents
  作者：Qun Li、Weibo Wang、Kristine B. Berst、Akiyo Claiborne、Lisa Hasvold、Kathleen Raye、Michael Tufano、Angela Nilius、Linus L. Shen、Robert Flamm、Jeff Alder、Kennan Marsh、DeAnne Crowell、Daniel T.W. Chu、Jacob J. Plattner

  DOI：10.1016/s0960-894x(98)00355-2

  日期：1998.8

  The 8-position side chain of 2-pyridones is believed to be involved in the binding with bacterial DNA gyrase to form the ternary complex, making them very important for the activity of 2-pyridones. A series of 2-pyridones having fluoro-substituted amines at the 8-position has been synthesized and their antibacterial activities and pharmacokinetic properties are reported. (C) 1998 Elsevier Science Ltd. All rights reserved.