methyl (2S)-2-[(2-amino-4-chloro-5-fluorophenyl)methyl-methylamino]propanoate | 890532-48-6

• 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: methyl (2S)-2-[(2-amino-4-chloro-5-fluorophenyl)methyl-methylamino]propanoate
• CAS: 890532-48-6
• 化学式: C₁₂H₁₆ClFN₂O₂
• 分子量: 274.723
• InChiKey: ARIZKWZLHUFVGT-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[(2-amino-4-chloro-5-fluorophenyl)methyl-methylamino]propanoate 、 6-乙酰氧基-4-氯-7-甲氧基喹唑啉 以 乙腈 为溶剂， 反应 4.0h， 以37%的产率得到methyl (2S)-2-[[2-[(6-acetyloxy-7-methoxyquinazolin-4-yl)amino]-4-chloro-5-fluorophenyl]methyl-methylamino]propanoate
  参考文献：
  名称：

  WO2006/61417

  摘要：

  公开号：
• 作为产物：
  描述：

  methyl (2S)-2-[(4-chloro-5-fluoro-2-nitrophenyl)methyl-methylamino]propanoate 在 铁粉 、 氯化铵 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以96%的产率得到methyl (2S)-2-[(2-amino-4-chloro-5-fluorophenyl)methyl-methylamino]propanoate
  参考文献：
  名称：

  WO2006/61417

  摘要：

  公开号：

文献信息

• MACROCYCLIC QUINAZOLE DERIVATIVES AND THEIR USE AS MTKI
  申请人：Freyne Eddy Jean Edgard

  公开号：US20100152174A1

  公开（公告）日：2010-06-17

  The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C 3-9 alkyl-, —C 1-5 alkyl-NR 13 —C 1-5 alkyl-, —C 1-5 alkyl-NR 14 —CO—C 1-5 alkyl-, —C 1-2 alkyl-NR 21 —H 2 —CO—NH—C 1-3 alkyl- or —C 1-2 alkyl-NR 23 —CO—CR 16 R 17 —NH—; X 1 represents O or —O—C 1-2 alkyl-; X 2 represents a direct bond, C 1-2 alkyl, —CO—C 1-2 alkyl or NR 12 —C 1-2 alkyl; R 1 represents hydrogen or halo; R 2 represents halo, acetylene or Het 1 ; R 3 represents hydrogen or cyano; R 4 represents Ar 4 —C 1-4 alkyloxy-, C 1-4 alkyloxy- or C 1-4 alkyloxy substituted with one or where possible two or more substituents selected from Het 2 , NR 7 R 8 , hydroxy and C 1-4 alkyloxy-C 1-4 alkyloxy-; R 7 represents hydrogen or C 1-4 alkyl; R 8 represents C 1-4 alkyl substituted with NR 25 R 26 or C 1-4 alkylsulfonyl; R 12 represents hydrogen or C 1-4 alkyl-; R 13 represents Ar 6 -sulfonyl or C 1-6 alkyloxycarbonyl optionally substituted with phenyl; R 16 and R 17 represents hydrogen, C 1-4 alkyl or R 16 and R 17 taken together with the carbon atom to which they are attached from a C 3-6 cycloalkyl; R 23 represents C 1-4 alkyl and R 23 represents hydrogen when R 16 and R 17 taken together with the carbon atom to which they are attached from a C 3-6 cycloalkyl; R 25 , R 26 , R 27 and R 28 each independently represent hydrogen or C 1-4 alkylcarbonyl; Het 1 represents 2 -bora- 1,3 -dioxolanyl; Het represents piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl or 1,1 -dioxothiomorpholinyl wherein said Het 2 is optionally substituted with C 1-4 alkyloxycarbonyl or NR 27 R 28 —C 1-4 alkyl; Ar 4 and Ar 5 represents phenyl; Ar 6 represents phenyl optionally substituted with nitro.

  本发明涉及式（I）化合物，其N-氧化物形式，药学上可接受的加成盐和立体化学异构体形式，其中Z代表NH; Y代表-C3-9烷基，-C1-5烷基-NR13-C1-5烷基，-C1-5烷基-NR14-CO-C1-5烷基，-C1-2烷基-NR21-H2-CO-NH-C1-3烷基或-C1-2烷基-NR23-CO-CR16R17-NH-; X1代表O或-O-C1-2烷基; X2代表直接键，C1-2烷基，-CO-C1-2烷基或NR12-C1-2烷基; R1代表氢或卤素; R2代表卤素，乙炔或Het1; R3代表氢或氰基; R4代表Ar4-C1-4烷氧基，C1-4烷氧基或C1-4烷氧基，其中可能有一或更多取代基选自Het2，NR7R8，羟基和C1-4烷氧基-C1-4烷氧基-; R7代表氢或C1-4烷基; R8代表C1-4烷基，取代为NR25R26或C1-4烷基磺酰基; R12代表氢或C1-4烷基-; R13代表Ar6-磺酰基或C1-6烷氧羰基，可选地取代苯基; R16和R17代表氢，C1-4烷基或R16和R17与它们连接的碳原子组成C3-6环烷基; R23代表C1-4烷基，当R16和R17与它们连接的碳原子组成C3-6环烷基时，R23代表氢; R25，R26，R27和R28分别独立地代表氢或C1-4烷基羰基; Het1代表2-硼-1,3-二氧杂环丙基; Het代表哌啶基，哌嗪基，吗啉基，硫代吗啉基或1,1-二氧硫代吗啉基，其中所述的Het2可选地取代为C1-4烷氧羰基或NR27R28-C1-4烷基; Ar4和Ar5代表苯基; Ar6代表可选地取代为硝基的苯基。
• Macrocyclic quinazole derivatives and their use as MTKI
  申请人：Janssen Pharmaceutica NV

  公开号：US10208062B2

  公开（公告）日：2019-02-19

  The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-2alkyl-NR21—H2—CO—NH—C1-3alkyl- or —C1-2alkyl-NR23—CO—CR16R17—NH—; X1 represents O or —O—C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, —CO—C1-2alkyl or NR12—C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1 R3 represents hydrogen or cyano; R4 represents Ar4—C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydrogen, C1-4alkyl or R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R23 represents C1-4alkyl and R23 represents hydrogen when R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R25, R26, R27 and R28 each independently represent hydrogen or C1-4alkylcarbonyl; Het1 represents 2-bora-1,3-dioxolanyl; Het2 represents piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl or 1,1-dioxothiomorpholinyl wherein said Het2 is optionally substituted with C1-4alkyloxycarbonyl or NR27R28—C1-4alkyl; Ar4 and Ar5 represents phenyl; Ar6 represents phenyl optionally substituted with nitro.

  本发明涉及式化合物 的 N-氧化物形式、药学上可接受的加成盐及其立体异构形式，其中 Z代表NH；Y代表-C3-9烷基-、-C1-5烷基-NR13-C1-5烷基-、-C1-5烷基-NR14-CO-C1-5烷基-、-C1-2烷基-NR21-H2-CO-NH-C1-3烷基-或-C1-2烷基-NR23-CO-CR16R17-NH-； X1 代表 O 或-O-C1-2烷基-； X2 代表直接键、C1-2烷基、-CO-C1-2烷基或 NR12-C1-2烷基； R1 代表氢或卤素； R2 代表卤素、乙炔或 Het1 R3 代表氢或氰基； R4 代表 Ar4-C1-4烷氧基-、C1-4烷氧基-或被选自 Het2、NR7R8、羟基和 C1-4 烷氧基-C1-4烷氧基-的一个或（如有可能）两个或多个取代基取代的 C1-4 烷氧基； R7 代表氢或 C1-4 烷基；R8 代表被 NR25R26 或 C1-4 烷基磺酰基取代的 C1-4 烷基； R12 代表氢或 C1-4 烷基-； R13 代表 Ar6-磺酰基或任选被苯基取代的 C1-6 烷氧基羰基； R16和R17代表氢、C1-4烷基或R16和R17连同它们所连接的碳原子来自C3-6环烷基； R23 代表 C1-4 烷基，当 R16 和 R17 与来自 C3-6 环烷基的碳原子连接在一起时，R23 代表氢； R25、R26、R27 和 R28 各自独立地代表氢或 C1-4 烷基羰基； Het1 代表 2-硼-1,3-二氧戊环； Het2 代表哌啶基、哌嗪基、吗啉基、硫代吗啉基或 1,1-二氧代硫代吗啉基，其中所述 Het2 任选被 C1-4 烷氧羰基或 NR27R28-C1-4 烷基取代； Ar4 和 Ar5 代表苯基；Ar6 代表任选被硝基取代的苯基。
• US20140256714A1
  申请人：——

  公开号：US20140256714A1

  公开（公告）日：2014-09-11
• US9688691B2
  申请人：——

  公开号：US9688691B2

  公开（公告）日：2017-06-27
• WO2006/61417
  申请人：——

  公开号：——

  公开（公告）日：——