benzyl (2S)-N-tert-butoxycarbonyl-4-trifluoromethyl-3,4-dehydroprolinate | 474417-77-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (2S)-N-tert-butoxycarbonyl-4-trifluoromethyl-3,4-dehydroprolinate
• 英文别名: 2-benzyl 1-(tert-butyl) (S)-4-(trifluoromethyl)-2.5-dihydro-1H-pyrrole-1.2-dicarboxylate；N-(tert-Butoxycarbonyl)-4-(trifluoromethyl)-3,4-didehydro-L-proline benzyl ester；2-O-benzyl 1-O-tert-butyl (2S)-4-(trifluoromethyl)-2,5-dihydropyrrole-1,2-dicarboxylate
• CAS: 474417-77-1
• 化学式: C₁₈H₂₀F₃NO₄
• 分子量: 371.356
• InChiKey: GMEUPKKQJBAJIJ-AWEZNQCLSA-N

物化性质

• 沸点：
  379.8±42.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-N-tert-butoxycarbonyl-4-trifluoromethyl-3,4-dehydroprolinate 在 10percent Pd/C 氢气 作用下， 以 乙醇 为溶剂， 以90%的产率得到(2S,4S)-N-叔丁氧基羰基-4-三氟甲基脯氨酸
  参考文献：
  名称：

  Practical Synthesis of Boc-Protected cis-4-Trifluoromethyl and cis-4-Difluoromethyl-l- prolines

  摘要：

  A short, efficient, and diastereomerically pure synthesis of N-Boc-cis-4-trifluoromethyl-L-proline (7) and N-Boc-cis-4-difluoromethyl-L-proline (9) from N-Boc-4-oxo-L-proline (4) is described. The reaction of 4 with Me3SiCF3 and the conversion of the carbonyl group of 4 into the difluoromethylene group are the key steps for the synthesis of 7 and 9, respectively.

  DOI：

  10.1021/jo0257400
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 吡啶 、 chromium(VI) oxide 、 氯化亚砜 、 四丁基氟化铵 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.33h， 生成 benzyl (2S)-N-tert-butoxycarbonyl-4-trifluoromethyl-3,4-dehydroprolinate
  参考文献：
  名称：

  Practical Synthesis of Boc-Protected cis-4-Trifluoromethyl and cis-4-Difluoromethyl-l- prolines

  摘要：

  A short, efficient, and diastereomerically pure synthesis of N-Boc-cis-4-trifluoromethyl-L-proline (7) and N-Boc-cis-4-difluoromethyl-L-proline (9) from N-Boc-4-oxo-L-proline (4) is described. The reaction of 4 with Me3SiCF3 and the conversion of the carbonyl group of 4 into the difluoromethylene group are the key steps for the synthesis of 7 and 9, respectively.

  DOI：

  10.1021/jo0257400

文献信息

• [EN] MALT1 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE MALT1 ET LEURS UTILISATIONS
  申请人：RHEOS MEDICINES INC

  公开号：WO2021207343A1

  公开（公告）日：2021-10-14

  The invention provides compounds of formula (I) wherein R1, R2, R3, R4 and R5 are as defined in the specification which are potent inhibitors of the enzyme MALT1 and are useful in the treatment of autoimmune disorders and diseases and as an immunooncology approach to the treatment of cancer, especially bladder cancer, colon cancer, hepatocellular cancer and small cell or non-small cell lung cancer.

  该发明提供了式（I）中的化合物，其中R1、R2、R3、R4和R5如规范中定义，它们是酶MALT1的有效抑制剂，可用于治疗自身免疫性疾病和疾病，并作为免疫肿瘤学治疗癌症的方法，特别是膀胱癌、结肠癌、肝细胞癌以及小细胞或非小细胞肺癌的治疗。
• Thrombin Inhibitors
  申请人：CHOBANIAN Harry

  公开号：US20150315141A1

  公开（公告）日：2015-11-05

  Compounds of the invention, which may be useful in inhibiting thrombin and associated thrombotic occlusions, have the following structure: or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; R is a heterocycle, —(CR 8 R 9 ) 1-2 NH 2 , or —(CR 8 R 9 ) 1-2 OH, wherein R 8 and R 9 , each time in which they occur, are independently H, C 1-6 alkyl, —CH 2 F, —CHF 2 , CF 3 or —CH 2 OH; W is a) —CHR 1 R 2 , where R 1 is —C(CH 3 ) 3 , and R 2 is —(CH 2 ) 1-2 OH, b) a 5- or 6-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N and O, wherein substituted heterocycle is substituted with R 3 , c) a 9- or 10-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N, O and S, wherein substituted heterocycle is mono-substituted with R 3 , or disubstituted with R 3 and R 4 , or d) a 3-, 4-, or 5-membered carbocyclic ring which is unsubstituted, mono-substituted with R 3 , di-substituted with R 3 and R 4 , or tri-substituted with R 3 , R 4 and R 5 ; R 3 is —CF 3 , —COOH, —COOR 7 , —C(O)R 6 , —CH(OH)R 6 , —CH 2 R 6 , R 6 , =O, halogen, R 7 , —OH, —NH 2 , or —NHSO 2 R 7 ; and R 10 is H or C 1-6 alkyl.

  本发明的化合物可用于抑制凝血酶和相关的血栓闭塞，具有以下结构：或其药学上可接受的盐，其中m为0或1；R是杂环，-(CR8R9)1-2NH2，或-(CR8R9)1-2OH，其中每次出现时R8和R9独立且为H、C1-6烷基、-CH2F、-CHF2、CF3或-CH2OH；W是a) -CHR1R2，其中R1为-C(CH3)3，R2为-(CH2)1-2OH，b) 1个或2个异原子从N和O中选择的5-或6-成员未取代或取代的杂环，其中取代的杂环取代为R3，c) 1个或2个异原子从N、O和S中选择的9-或10-成员未取代或取代的杂环，其中取代的杂环为单取代的R3，或双取代的R3和R4，或d) 未取代的3-、4-或5-成员碳环，单取代的R3，双取代的R3和R4，或三取代的R3、R4和R5；R3为-CF3、-COOH、-COOR7、-C（O）R6、-CH（OH）R6、-CH2R6、R6、=O、卤素、R7、-OH、-NH2或-NHSO2R7；R10为H或C1-6烷基。
• Synthesis of <i>cis-</i>4-Trifluoromethyl- and <i>cis</i>-4-Difluoromethyl-<scp>l</scp>-pyroglutamic Acids
  作者：Xiao-Long Qiu、Feng-Ling Qing

  DOI：10.1021/jo034098m

  日期：2003.5.1

  Efforts to synthesize 4-trifluoromethyl- and 4-difluoromethyl-L-pyroglutamic acids are described. After many arduous efforts, we successfully synthesized our target molecules cis-4-trifluoromethyl-L-pyroglutamic acid 25 and cis-4-difluoromethyl-L-pyroglutamic acid 26 from trams-4-hydroxy-L-proline through oxidation of fluorinated prolinates with RuO4.
• THROMBIN INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2922535B1

  公开（公告）日：2021-11-10
• US9469608B2
  申请人：——

  公开号：US9469608B2

  公开（公告）日：2016-10-18