Sodium Bicarbonate → 5-(3-(2-methoxyphenyl)-1H-pyrrolo(2,3-b)pyridin-5-yl)-N,N-dimethylpyridine-3-carboxamide

HRID 901360Notes

Reaction equation

HRID 901360 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1.Br[C:38]1[CH:39]=[N:40][CH:41]=[C:42]([CH:48]=1)[C:43]([N:45]([CH3:47])[CH3:46])=[O:44].C([O-])(O)=O.[Na+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:38]3[CH:39]=[N:40][CH:41]=[C:42]([CH:48]=3)[C:43]([N:45]([CH3:46])[CH3:47])=[O:44])[CH:16]=2)[NH:11][CH:10]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 234370495-Bromo-N,N-dimethylpyridine-3-carboxamide

Product 1

HCID 167500945-(3-(2-methoxyphenyl)-1H-pyrrolo(2,3-b)pyridin-5-yl)-N,N-dimethylpyridine-3-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a 5 mL Personal Chemistry microwave reaction vial were added 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (0.136 g, 0.270 mmol), 5-Bromo-N,N-dimethyl-nicotinamide (0.0756 g, 0.332 mmol; preparation described below), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (16.2 mg, 0.01 mmol), acetonitrile (2 mL) and saturated aqueous NaHCO3 (2 mL). The vial was sealed, purged with N2, and irradiated in a Personal Chemistry Optimizer at 90° C. for 15 min. The layers were separated, and the aqueous phase was extracted 3× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in 3:1 MeOH/acetone (4 mL total) and treated with 500 μL of 50% w/w KOH(aq) for 1 h. Glacial Acetic acid was added to obtain pH 7, then the reaction mixture was concentrated. The residue was partitioned between EtOAc and water, then the layers were separated, and the organic phase was washed 2× with water. The organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate (containing 10% MeOH) and hexanes afforded the title compound as a tan powder (57 mg, 57%). 1H-NMR (500 MHz, d6-DMSO) δ=11.96 (br. s, 1H), 8.95 (d, J=2.5 Hz, 1H), 8.56 (d, J=2.0 Hz, 1H), 8.52 (d, J=2.0 Hz, 1H), 8.24 (d, J=2.0 Hz, 1H), 8.13 (t, J=2.0 Hz, 1H), 7.72 (d, J=3.0 Hz, 1H), 7.59 (dd, J=2.0, 5.5 Hz, 1H), 7.25 (dd, J=1, 7.5 Hz,1H), 7.08 (d, J=7.5 Hz, 1H), 6.99 (t, J=7.5 Hz, 1H), 3.76 (s, 3H), 2.97 (s, 3H), 2.92 (s, 3H); MS: m/z 373.1 [MH+].

Workup

  1. customInto a 5 mL Personal Chemistry microwave reaction
  2. customThe vial was sealed
  3. custompurged with N2
  4. customirradiated in a Personal Chemistry Optimizer at 90° C. for 15 min
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted 3× with EtOAc
  7. additionThe combined organic phase was treated with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe crude product was dissolved in 3:1 MeOH/acetone (4 mL total)
  12. additiontreated with 500 μL of 50% w/w KOH(aq) for 1 h
  13. additionGlacial Acetic acid was added
  14. customto obtain pH 7
  15. concentrationthe reaction mixture was concentrated
  16. customThe residue was partitioned between EtOAc and water
  17. customthe layers were separated
  18. washthe organic phase was washed 2× with water
  19. additionThe organic phase was treated with brine
  20. dry with materialdried (Na2SO4)
  21. filtrationfiltered
  22. concentrationconcentrated
  23. customPurification by flash silica gel chromatography

Sources & evidence

ORD record
ord-61373b3182924b18bfb22a8b550354b5
Source dataset
uspto-grants-2008_04
Patent number
US07361763B2

Reaction notes

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