N,N'-Dimethylethylenediamine → 4-Fluoro-N-{[2-oxo-6-(1H-1,2,4-triazol-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

HRID 1878028Notes

Reaction equation

HRID 1878028 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:10](CC3C=CC(OC)=CC=3)[C:9](=[O:20])[O:8][C:7]([CH2:25][NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)([C:21]([F:24])([F:23])[F:22])[C:6]=2[CH:36]=1.[NH:37]1[CH:41]=[N:40][CH:39]=[N:38]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>CN(C=O)C.C(OCC)(=O)C.[Cu](I)I>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:27]([NH:26][CH2:25][C:7]2([C:21]([F:22])([F:23])[F:24])[C:6]3[CH:36]=[C:2]([N:37]4[CH:41]=[N:40][CH:39]=[N:38]4)[CH:3]=[CH:4][C:5]=3[NH:10][C:9](=[O:20])[O:8]2)=[O:35])=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 92571H-1,2,4-TriazoleHCID 62657Potassium Phosphate, TribasicHCID 44549927N-{[6-iodo-1-(4-methoxybenzyl)-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide

Product 1

HCID 445503754-Fluoro-N-{[2-oxo-6-(1H-1,2,4-triazol-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A solution of N-{[6-iodo-1-(4-methoxybenzyl)-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide (50 mg, 0.081 mmol), 1,2,4-triazole (16.9 mg, 0.244 mmol), potassium phosphate (25.9 mg, 0.122 mmol), N,N′-dimethylethylenediamine (6.9 μL, 0.065 mmol) and copper iodide (I) (3.1 mg, 0.016 mmol) in DMF (0.4 mL) was stirred for 1 hour under heating at 110° C. The temperature of the solution was brought to room temperature, and the solution was diluted with ethyl acetate, which was washed sequentially with a saturated aqueous ammonium chloride solution 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 residue was subjected to the same condition as in Example 154 to effect deprotection of the 4-methoxybenzyl group, whereby the objective compound (8.0 mg, 23%) was obtained as a pale white solid.

Workup

  1. customwas brought to room temperature
  2. washwas washed sequentially with a saturated aqueous ammonium chloride solution and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customAfter the drying agent was removed by filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customwas obtained as a pale white solid

Sources & evidence

ORD record
ord-71d299347fea4b629b89c9bad2ebbd4d
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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