P-Anisidine → 2-(2,6-Difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamide

HRID 389748Notes

Reaction equation

HRID 389748 reaction equation
Br[C:2]1[O:6][C:5]([C:7]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][C:8]=2[F:14])=[N:4][C:3]=1[C:15]([NH2:17])=[O:16].CC(C)([O-])C.[Na+].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1>FC(F)(F)C1C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:14][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([F:13])[C:7]=1[C:5]1[O:6][C:2]([NH:32][C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)=[C:3]([C:15]([NH2:17])=[O:16])[N:4]=1

Participants

6

Reactant 3

HCID 7732P-AnisidineHCID 23676156Sodium t-butoxideHCID 595875995-Bromo-2-(2,6-difluorophenyl)oxazole-4-carboxamide

Product 1

HCID 595874272-(2,6-Difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamideYield 8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7368(Trifluoromethyl)benzeneSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred, degassed solution of 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carboxamide (0.125 g, 0.41 mmol) in trifluorotoluene (10.5 mL) was added tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.02 mmol), (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (0.026 g, 0.04 mmol), and sodium tert-butoxide (0.059 g, 0.62 mmol). This was followed by addition of p-anisidine (0.076 g, 0.62 mmol) after approximately 3 minutes stirring. The resulting reaction mixture was degassed, placed under an N2 atmosphere and heated in the microwave at 160° C. for 20 minutes. The solution was then washed with 2M aqueous HCl and brine, dried over MgSO4 and then passed through a MP-SH resin cartridge (500 mg). The solvent was removed in vacuo and the residue purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamide (0.0037 g, 0.01 mmol, 8%) as a white solid. 1H NMR (DMSO) δ 3.74 (3H, s), 6.93 (2H, d), 7.29 (2H, br. s), 7.32 (2H, t), 7.37 (2H, d), 7.62 (1H, m), 9.17 (1H, br. s). LCMS (2) Rt: 2.80 min; m/z (ES+) 346.

Workup

  1. customThe resulting reaction mixture
  2. customwas degassed
  3. washThe solution was then washed with 2M aqueous HCl and brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-9cf0b62109f6464999b6db6b52f21b86
Source dataset
uspto-grants-2013_02
Patent number
US08378095B2

Reaction notes

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