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

HRID 1410478Notes

Reaction equation

HRID 1410478 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-5c30c87ca7ef40fc88baca9d3ac56593
Source dataset
uspto-grants-2014_12
Patent number
US08921544B2

Reaction notes

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