Hydrochloric Acid → 4-Fluoro-N-{[2-oxo-6-(1H-pyrazol-5-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

HRID 1878018Notes

Reaction equation

HRID 1878018 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([CH2:16][NH:17][C:18](=[O:26])[C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)([C:12]([F:15])([F:14])[F:13])[C:6]=2[CH:27]=1.O1CCCCC1[N:34]1[C:38](B(O)O)=[CH:37][CH:36]=[N:35]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>CN(C=O)C.O.C(OCC)(=O)C>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:18]([NH:17][CH2:16][C:7]2([C:12]([F:15])([F:14])[F:13])[C:6]3[CH:27]=[C:2]([C:36]4[NH:35][N:34]=[CH:38][CH:37]=4)[CH:3]=[CH:4][C:5]=3[NH:10][C:9](=[O:11])[O:8]2)=[O:26])=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 18407952Tripotassium phosphate trihydrateHCID 44549926N-{[6-bromo-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamideHCID 467394631-(Tetrahydropyran-2-yl)pyrazole-5-boronic acid

Product 1

HCID 252547234-Fluoro-N-{[2-oxo-6-(1H-pyrazol-5-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-{[6-Bromo-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide (4.0 g, 8.94 mmol), [1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]boronic acid (2.63 g, 13.42 mmol), a palladium chloride-1,1-bis(diphenylphosphino)ferrocene complex (654 mg, 0.894 mmol) and potassium phosphate trihydrate (4.76 g, 17.88 mmol) were suspended in DMF (27 mL) and water (2.7 mL), and the mixed solution was stirred at 120° C. for 15 minutes under microwave irradiation. After the reaction solution was left to cool, water (10 mL) and concentrated hydrochloric acid (5 mL) were sequentially added thereto, and the solution was stirred at room temperature for 2 hours. The solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1). The resulting foamy solid was recrystallized from ethyl acetate-heptane, whereby the objective compound (2.70 g, 69.5%) was obtained as a white solid.

Workup

  1. waitAfter the reaction solution was left
  2. temperatureto cool
  3. customthe organic layer was separated
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter the drying agent was removed by filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1)
  9. customThe resulting foamy solid was recrystallized from ethyl acetate-heptane, whereby the objective compound (2.70 g, 69.5%)
  10. customwas obtained as a white solid

Sources & evidence

ORD record
ord-f5a3ac3c2a13437593b103d2b461e9e2
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

Loading…