Sodium Carbonate → HCID 59824952, compound

HRID 886572Notes

Reaction equation

HRID 886572 reaction equation
[CH3:1][N:2]([CH3:22])[C:3](=[O:21])[C:4](=[O:20])[C:5]1[CH:6]=[N:7][CH:8]=[C:9](B2OC(C)(C)C(C)(C)O2)[CH:10]=1.Br[C:24]1[CH:25]=[C:26]2[C:32]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[O:39][CH3:40])=[CH:31][NH:30][C:27]2=[N:28][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].O=[N-]>C(#N)C>[CH3:40][O:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:32]1[C:26]2[C:27](=[N:28][CH:29]=[C:24]([C:9]3[CH:10]=[C:5]([C:4](=[O:20])[C:3]([N:2]([CH3:1])[CH3:22])=[O:21])[CH:6]=[N:7][CH:8]=3)[CH:25]=2)[NH:30][CH:31]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 3001380Nitrate(1-), oxo-HCID 596997875-Bromo-3-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridineHCID 67280283HCID 67280283, compound

Product 1

HCID 59824952HCID 59824952, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

Crude N,N-dimethyl-2-oxo-2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)acetamide (592 g, 1.32 mol) from the boronic ester synthesis and 5-bromo-3-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine 7 (398.5 g, 1.32 mol) were stirred in acetonitrile (5 L) in 10 L reaction vessel. The solution was stirred and purged with N2 for 30 min. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (34 g, 40.8 mmol) and Na2CO3(aq) (312.8 g dissolved in 1.36 L H2O) were added. Stirring and purging with N2 continued for 30 min. Thereafter, the solution was heated to 75° C. and stirred under N2 for two days. After the conversion was confirmed to be complete by NMR, H2O (1700 ml) was added and stirring was continued for 10 min. Then heating was stopped and the reaction mixture was filtered over a pad of Celite®. The Celite® pad was washed with a 1:1 mixture of acetonitrile/H2O (3×1000 ml). The filtrate was concentrated until almost acetonitrile had evaporated and a brownish precipitate formed. The concentrated mixture was then extracted with CH2Cl2 (1×3.6 L, 2×1000 ml). The organic layers were combined and dried over Na2SO4, after which the solvent was evaporated in vacuo. The residue was treated with 1800 ml MeOH and sonicated for 15 minutes. The yellowish solid is filtered off and dried in vacuo. This solid is dissolved in a mixture of 10% MeOH in CH2Cl2 and filtered over a SiO2 plug, and washed off using 10% MeOH in CH2Cl2 (±15 L). Yielding after evaporation of the solvent in vacuo ketoamide (380 g, 0.95 mol, 72% over two steps).

Workup

  1. custompurged with N2 for 30 min
  2. stirringStirring
  3. custompurging with N2
  4. stirringstirred under N2 for two days
  5. additionwas added
  6. stirringstirring
  7. waitwas continued for 10 min
  8. temperatureThen heating
  9. filtrationthe reaction mixture was filtered over a pad of Celite®
  10. washThe Celite® pad was washed with a 1:1 mixture of acetonitrile/H2O (3×1000 ml)
  11. concentrationThe filtrate was concentrated until almost acetonitrile
  12. customhad evaporated
  13. customa brownish precipitate formed
  14. extractionThe concentrated mixture was then extracted with CH2Cl2 (1×3.6 L, 2×1000 ml)
  15. dry with materialdried over Na2SO4
  16. customafter which the solvent was evaporated in vacuo
  17. additionThe residue was treated with 1800 ml MeOH
  18. customsonicated for 15 minutes
  19. filtrationThe yellowish solid is filtered off
  20. customdried in vacuo
  21. dissolutionThis solid is dissolved in a mixture of 10% MeOH in CH2Cl2
  22. filtrationfiltered over a SiO2 plug
  23. washwashed off
  24. customYielding

Sources & evidence

ORD record
ord-a1e083261b8f4d0fac7c2932b0a80a66
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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