Triethylamine → 2-bromo-N-(4-fluorobenzyl)-5-methoxyisonicotinamide

HRID 2201536Notes

Reaction equation

HRID 2201536 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[Br:19][C:20]1[CH:21]=[C:22]([C:26]([O:29][CH3:30])=[CH:27][N:28]=1)[C:23]([OH:25])=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]=[C:22]([C:26]([O:29][CH3:30])=[CH:27][N:28]=1)[C:23]([NH:39][CH2:38][C:35]1[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=1)=[O:25]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 111923Propylphosphonic anhydrideHCID 714639642-Bromo-5-methoxyisonicotinic acid

Product 1

HCID 1177718312-bromo-N-(4-fluorobenzyl)-5-methoxyisonicotinamideYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

T3P (2.4 g, 7.4 mmol) was added to a solution of 2-bromo-5-methoxyisonicotinic acid (1.0 g, 3.7 mmol), (4-fluorophenyl)methanamine (466 mg, 3.7 mmol) and Et3N (1.1 g, 11.1 mmol) in DCM (10 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=2:1) to give the product of compound 2-bromo-N-(4-fluorobenzyl)-5-methoxyisonicotinamide (1.1 g, yield: 92%). 1H-NMR (CDCl3, 400 MHz) δ 8.18 (d, J=2.8 Hz, 2H), 7.96 (s, 1H), 7.31 (dd, J=5.2, 8.4 Hz, 2H), 7.04 (t, J=8.8 Hz, 2H), 4.61 (d, J=6.0 Hz, 2H), 4.03 (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=2:1)

Sources & evidence

ORD record
ord-2887c9525e41468e9fd80477d7ce7e27
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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