Hydroxylamine → (S)-3-methyl-2-(6-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)-[1,4]oxazepan-4-yl)-6-(pyrimidin-4-yl)pyrimidin-4(3H)-one

HRID 515468Notes

Reaction equation

HRID 515468 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[N:15]1[CH2:21][C@H:20]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[CH2:19][O:18][CH2:17][CH2:16]1.NO.[CH2:32]([N:34](CC)CC)[CH3:33].C(OC(=O)C)(=[O:41])C>C(O)C.CN(C)C=O>[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[N:15]1[CH2:21][C@H:20]([C:22]2[CH:29]=[CH:28][C:25]([C:26]3[N:34]=[C:32]([CH3:33])[O:41][N:27]=3)=[CH:24][CH:23]=2)[CH2:19][O:18][CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 46935963(S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrile

Product 1

HCID 67282002(S)-3-methyl-2-(6-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)-[1,4]oxazepan-4-yl)-6-(pyrimidin-4-yl)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrile (183 mg, 0.471 mmol) in ethanol (0.95 ml) was added 50 wt. %—hydroxylamine aqueous solution (96.4 mg, 1.46 mmol) at room temperature. The mixture was stirred at 80° C. for 2 hours and concentrated. The residue was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. N,N-dimethylformamide (0.95 ml), triethylamine (143 mg, 1.41 mmol) and acetic anhydride (62.5 mg, 0.612 mmol) was added to the residue at 0° C. The mixture was stirred at room temperature. After 2 hours, the mixture was heated to 135° C. and stirred for 2 hours. The resulting mixture cooled to room temperature was partitioned between water and chloroform. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3) to afford (S)-3-methyl-2-(6-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)-[1,4]oxazepan-4-yl)-6-(pyrimidin-4-yl)pyrimidin-4(3H)-one (A085) as white solid (126 mg, 60%).

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. stirringThe mixture was stirred at room temperature
  6. waitAfter 2 hours
  7. temperaturethe mixture was heated to 135° C.
  8. stirringstirred for 2 hours
  9. temperatureThe resulting mixture cooled to room temperature
  10. customwas partitioned between water and chloroform
  11. washThe organic layer was washed with brine
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3)

Sources & evidence

ORD record
ord-84685bc1a6114d15a363d9a1db778bcd
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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