Potassium Phosphate, Tribasic → 2-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

HRID 1472558Notes

Reaction equation

HRID 1472558 reaction equation
[Br:1][C:2]1[C:3](I)=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:10][C:11]1[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=1[C:13]([NH:15][O:16][CH3:17])=[O:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[Br:1][C:2]1[C:3]([NH:10][C:11]2[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=2[C:13]([NH:15][O:16][CH3:17])=[O:14])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 123927072-Amino-N-methoxybenzamideHCID 218651405-Bromo-2-chloro-4-iodopyridine

Product 1

HCID 575169052-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-bromo-2-chloro-4-iodo-pyridine (5 g, 15.72 mmole, 1 eq), 2-amino-N-methoxy-benzamide (2.61 g, 15.72 mmole, 1 eq) and K3PO4 (8.34 g, 39.3 mmole, 2.5 eq), and 1,4-dioxane (30 mL) was degassed with N2 for 1 h. To this was added DPEPhos (0.67 g, 1.25 mmole, 0.08 eq) and Pd(OAc)2 (0.07 g, 0.31 mmole, 0.02 eq) and this mixture was degassed again with N2 for 30 min. The resulting mixture was refluxed for overnight. After completion of reaction, solvent was removed under reduced pressure and residue was diluted with water (100 mL) and extracted with 5% MeOH-DCM (3×100 mL). Combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude compound. It was purified by column chromatography over silica gel (60-120 mesh) using 20% Ethyl acetate-hexane as the eluant to yield the title compound as off white solid (3.5 g, 62%). 1H-NMR (400 MHz, DMSO-d6): δ 3.56 (s, 3H), 6.88-6.98 (m, 1H), 7.08 (s, 1H), 7.17-7.25 (m, 1H), 7.26-7.35 (m, 1H), 7.82-7.90 (m, 1H), 8.23 (s, 1H), 12.86 (brs, 1H). LC-MS [M+H]+=356.30.

Workup

  1. customwas degassed with N2 for 1 h
  2. customthis mixture was degassed again with N2 for 30 min
  3. temperatureThe resulting mixture was refluxed for overnight
  4. customAfter completion of reaction, solvent
  5. customwas removed under reduced pressure and residue
  6. additionwas diluted with water (100 mL)
  7. extractionextracted with 5% MeOH-DCM (3×100 mL)
  8. dry with materialCombined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a crude compound
  12. customIt was purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-928cbc63ed4d43c5aad0fb7f41c8ef99
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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