Triethylamine → 2-Bromo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]pyridine-5-carboxamide

HRID 355735Notes

Reaction equation

HRID 355735 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[CH:4][N:3]=1.C(N(CC)CC)C.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=1[N:27]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1>S(Cl)(Cl)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:26][C:23]2[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[C:21]([N:27]3[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]3)[CH:22]=2)=[O:10])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2389326-Bromonicotinic acidHCID 103311014-Methoxy-3-(4-methylpiperazin-1-yl)aniline

Product 1

HCID 189406772-Bromo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]pyridine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

2-Bromo-5-pyridinecarboxylic acid (0.34 g; 1.68 mmol) was heated at reflux in thionyl chloride (8 ml) for 1 hour, cooled, evaporated in vacuo and the residue azeotroped with toluene. The orange residue was redissolved in CH2Cl2 (6 ml) and treated with dry triethylamine (0.24 ml;1.68 mmol) and 4-methoxy-3-(4-methyl-1-piperazinyl)benzenamine (0.372 g;1.68 mmol). The solution was stirred under Ar (18 hours), evaporated in vacuo and partitioned satd. K2CO3 (aq)/EtOAc. The organic phases were combined, dried over Na2SO4, filtered and the filtrate evaporated in vacuo to a brown gum. The gum was purified by flash silica-gel chromatography and eluted with 3%MeOH/CHCl3 to yield the title compound as brown crystals after trituration with acetone/Et2O (0.13 g;19%).

Workup

  1. temperaturecooled
  2. customevaporated in vacuo
  3. customthe residue azeotroped with toluene
  4. dissolutionThe orange residue was redissolved in CH2Cl2 (6 ml)
  5. customevaporated in vacuo
  6. custompartitioned
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe filtrate evaporated in vacuo to a brown gum
  10. customThe gum was purified by flash silica-gel chromatography
  11. washeluted with 3%MeOH/CHCl3

Sources & evidence

ORD record
ord-5f41f94c52f94b43ba7ffc40dad64070
Source dataset
uspto-grants-1998_11
Patent number
US05834471

Reaction notes

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