Triethylamine → 5-Bromo-N-(4-fluorobenzyl)-2-methoxynicotinamide

HRID 2201540Notes

Reaction equation

HRID 2201540 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[Br:19][C:20]1[CH:21]=[N:22][C:23]([O:29][CH3:30])=[C:24]([CH:28]=1)[C:25]([OH:27])=O.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH2:39])=[CH:34][CH:33]=1.CCN(CC)CC>C(Cl)Cl.O>[Br:19][C:20]1[CH:21]=[N:22][C:23]([O:29][CH3:30])=[C:24]([CH:28]=1)[C:25]([NH:39][CH2:38][C:35]1[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=1)=[O:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 111923Propylphosphonic anhydrideHCID 143717285-Bromo-2-methoxypyridine-3-carboxylic acid

Product 1

HCID 1177715975-Bromo-N-(4-fluorobenzyl)-2-methoxynicotinamideYield 91.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

T3P (8.2 g, 25.8 mmol) was added to a solution of 5-bromo-2-methoxynicotinic acid (3 g, 12.9 mmol), (4-fluorophenyl)methanamine (1.6 g, 12.9 mmol) and Et3N (3.9 g, 38.7 mmol) in DCM (50 mL) at 0° C. The mixture was stirred at RT for 1 h. Water (50 mL) was added and the mixture was extracted with DCM. The organic layer was washed with brine and dried over Na2SO4. After being concentrated, the residue was purified by column chromatography (PE:EtOAc=4:1) to give the product of 5-bromo-N-(4-fluorobenzyl)-2-methoxynicotinamide (4.0 g, yield: 91%). 1H-NMR (CDCl3, 400 MHz) δ 8.64 (d, J=2.4 Hz, 1H), 8.31 (d, J=2.4 Hz, 1H), 8.17 (s, 1H), 7.32 (dd, J=5.2, 8.4 Hz, 2H), 7.04 (t, J=8.8 Hz, 2H), 4.63 (d, J=6.0 Hz, 2H), 4.05 (s, 3H). MS (M+H)+: 339/341

Workup

  1. extractionthe mixture was extracted with DCM
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationAfter being concentrated
  5. customthe residue was purified by column chromatography (PE:EtOAc=4:1)

Sources & evidence

ORD record
ord-199efcd436eb4723a6e9fc52b4a269d3
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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