3-Fluoroaniline → HCID 67390628, compound

HRID 913293Notes

Reaction equation

HRID 913293 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[F:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:21][C:22]1[CH:23]=[C:24]([NH:25][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 97423-FluoroanilineHCID 10796Cesium carbonateHCID 86646778HCID 86646778, compound2×

Product 1

HCID 67390628HCID 67390628, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine (i.e., the product of Step A) (500 mg, 1.7 mmol) in toluene (15 mL) was added 3-fluoroaniline (400 uL, 4.1 mmol), palladium(II) acetate (50 mg, 0.20 mmol), (±)-BINAP (100 mg, 0.16 mmol) and cesium carbonate (1.9 g, 5.8 mmol), and the resulting mixture was stirred at reflux for 4.5 h. The cooled mixture was partitioned between ethyl acetate and water, and the organic layer was washed with brine, dried over MgSO4 and filtered. The solvent was removed under reduced pressure to give a residue that was chromatographed on silica gel eluted with 15% to 85% ethyl acetate in hexanes to afford 330 mg of title compound as a solid, m.p. 190-192° C.

Workup

  1. temperatureat reflux for 4.5 h
  2. customThe cooled mixture was partitioned between ethyl acetate and water
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customto give a residue that
  8. customwas chromatographed on silica gel
  9. washeluted with 15% to 85% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-90272158a6d74f8d8230d6b431cdab56
Source dataset
uspto-grants-2011_09
Patent number
US08026359B2

Reaction notes

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