Carbonic acid sodium salt (1:2) → [3-Amino-6-(1h-indol-5-yl)-pyrazin-2-yl]-pyridin-3-yl-methanone

HRID 81460

反应方程式

HRID 81460 反应方程式
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:31][C:32]1[C:33]([C:39]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)=[O:40])=[N:34][C:35](Br)=[CH:36][N:37]=1.B(O)(O)[C:48]1[NH:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=1.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.C([O-])(O)=O.[Na+].C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.C(O)C>[NH2:31][C:32]1[C:33]([C:39]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)=[O:40])=[N:34][C:35]([C:52]2[CH:51]=[C:50]3[C:55](=[CH:54][CH:53]=2)[NH:56][CH:48]=[CH:49]3)=[CH:36][N:37]=1

参与物

9

反应物 4

HCID 10340Carbonic acid sodium salt (1:2)HCID 821241,4-双(二苯基膦)丁烷HCID 225673581H-吲哚-2-硼酸HCID 86634541(3-Amino-6-bromo-pyrazin-2-yl)-pyridin-3-yl-methanone

产物 1

HCID 44233093[3-Amino-6-(1h-indol-5-yl)-pyrazin-2-yl]-pyridin-3-yl-methanone

试剂、催化剂与溶剂 4

HCID 498840二(氰基苯)二氯化钯催化剂HCID 702乙醇溶剂HCID 8857乙酸乙酯溶剂HCID 516892碳酸氢钠溶剂

实验过程

Bis(benzonitrile)palladium(II)chloride (5.2 mg, 0.013 mmol) and 1,4-bis(diphenylphosphino)butane (6.7 mg, 0.015 mmol) in toleune (0.6 ml) are stirred for 20 minutes. (3-Amino-6-bromo-pyrazin-2-yl)-pyridin-3-yl-methanone (Intermediate AA) (0.075 g, 0.27 mmol), 5-indoylboronic acid (0.056 g, 0.35 mmol), ethanol (0.36 ml) and 1M Na2CO3 (0.65 ml) are added and the reaction is heated using microwave radiation at 140° C. for 20 minutes. The mixture is diluted with EtOAc and sat. aq. NaHCO3. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic extracts are dried (MgSO4), and purified by preperative HPLC (0-100% MeCN in water −0.1% TFA) to yield the title compound as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ11.27 (1H, s), 9.21 (1H, s), 9.09 (1H, s), 8.86 (1H, dd), 8.39-8.41 (1H, dt), 8.19 (1H, s), 7.99 (2H, s), 7.65-7.73 (2H, m), 7.5 (1H, d), 7.44 (1H, t), 6.53 (1H, s). MS ink 316 [M+H]+

后处理

  1. temperaturethe reaction is heated
  2. customat 140° C.
  3. customfor 20 minutes
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with EtOAc
  6. dry with materialThe combined organic extracts are dried (MgSO4)
  7. custompurified by preperative HPLC (0-100% MeCN in water −0.1% TFA)

来源与证据

ORD记录
ord-70ac452ddcf34943b58bbf6379b1e39b
来源数据集
uspto-grants-2014_09
专利号
US08846687B2

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