Ethanol → HCID 136337197, compound

HRID 1878025Notes

Reaction equation

HRID 1878025 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:25]([F:28])([F:27])[F:26])[C:15]3[CH:16]=[C:17](C(NC)=O)[CH:18]=[CH:19][C:14]=3[NH:13][C:12](=[O:24])[O:11]2)=[O:7])=[CH:4][CH:3]=1.C1N=CN([C:36]([N:38]2[CH:42]=[N:41]C=C2)=[O:37])C=1.C([OH:45])C>NO.C(OCC)(=O)C>[F:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:25]([F:27])([F:28])[F:26])[C:15]3[CH:16]=[C:17]([C:42]4[NH:38][C:36](=[O:45])[O:37][N:41]=4)[CH:18]=[CH:19][C:14]=3[NH:13][C:12](=[O:24])[O:11]2)=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 682631,1'-CarbonyldiimidazoleHCID 68490661HCID 68490661, compound

Product 1

HCID 136337197HCID 136337197, compound

Reagents, catalysts & solvents 2

HCID 787HydroxylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N-{[6-cyano-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide (50 mg, 0.127 mmol) synthesized in Example 159 in ethanol (0.5 mL), hydroxylamine (50% aqueous solution, 40 μL) was added, and the solution was stirred overnight at room temperature. The solution was diluted with ethyl acetate, which was washed sequentially with water and saturated brine and then dried over magnesium sulfate. The residue was dissolved in dioxane (1 mL), and under stirring the solution at room temperature, CDI (41 mg, 0.25 mmol) was added thereto. After the reaction solution was stirred at 90° C. for 3 hours, the temperature of the solution was brought to room temperature. Then, the solution was diluted with ethyl acetate, which was washed sequentially with water, 1 N hydrochloric acid and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the residue was crystallized with ethanol and water, whereby the objective compound (18 mg, 31%) was obtained as a white solid.

Workup

  1. washwas washed sequentially with water and saturated brine
  2. dry with materialdried over magnesium sulfate
  3. dissolutionThe residue was dissolved in dioxane (1 mL)
  4. stirringunder stirring the solution at room temperature
  5. stirringAfter the reaction solution was stirred at 90° C. for 3 hours
  6. customwas brought to room temperature
  7. washwas washed sequentially with water, 1 N hydrochloric acid and saturated brine
  8. dry with materialdried over magnesium sulfate
  9. customAfter the drying agent was removed by filtration
  10. customthe residue was crystallized with ethanol and water, whereby the objective compound (18 mg, 31%)
  11. customwas obtained as a white solid

Sources & evidence

ORD record
ord-44b07d08068442acbaebe13e2cd6fbf5
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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