Sodium Carbonate → [3-Amino-6-(1h-indol-5-yl)-pyrazin-2-yl]-pyridin-3-yl-methanone

HRID 81460

Reaction equation

HRID 81460 reaction equation
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

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 821241,4-Bis(diphenylphosphino)butaneHCID 225673581H-Indol-2-ylboronic acidHCID 86634541(3-Amino-6-bromo-pyrazin-2-yl)-pyridin-3-yl-methanone

Product 1

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

Reagents, catalysts & solvents 4

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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]+

Workup

  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)

Sources & evidence

ORD record
ord-70ac452ddcf34943b58bbf6379b1e39b
Source dataset
uspto-grants-2014_09
Patent number
US08846687B2

Linked notes

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