Bromoacetonitrile → HCID 117677158, compound

HRID 570920Notes

Reaction equation

HRID 570920 reaction equation
[CH3:1][C:2]1([CH3:23])[O:6][N:5]=[C:4]([C:7]2[CH2:8][N:9](/[N:14]=[CH:15]/[C:16]3[CH:17]=[N:18][CH:19]=[C:20]([F:22])[CH:21]=3)[C:10](=[O:13])[NH:11][N:12]=2)[CH2:3]1.[H-].[Na+].Br[CH2:27][C:28]#[N:29]>C1COCC1>[CH3:1][C:2]1([CH3:23])[O:6][N:5]=[C:4]([C:7]2[CH2:8][N:9](/[N:14]=[CH:15]/[C:16]3[CH:17]=[N:18][CH:19]=[C:20]([F:22])[CH:21]=3)[C:10](=[O:13])[N:11]([CH2:27][C:28]#[N:29])[N:12]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 89601647HCID 89601647, compound

Product 1

HCID 117677158HCID 117677158, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-(5,5-dimethyl-4H-isoxazol-3-yl)-4-[(E)-(5-fluoro-3-pyridyl)methyleneamino]-2,5-dihydro-1,2,4-triazin-3-one (150 mg, 0.471 mmol) in anhydrous THF (8.0 mL) was added NaH (28.2 mg, 0.707 mmol) at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 10 min followed by dropwise addition of 2-bromoacetonitrile (36.2 μL, 62.2 mg, 0.518 mmol). The reaction mixture was allowed to warm to room temp. and stirring was continued for 2 h. The reaction mixture was quenched by addition of methanol followed by ice. The organic layer was evaporated in rotavap and aqueous layer extracted with ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to furnish the crude product. Purification by flash chromatography (60-70% EtOAc/hexanes) provided the desired product as a white solid. M.p. 195-197° C.

Workup

  1. temperatureto warm to room temp.
  2. stirringstirring
  3. waitwas continued for 2 h
  4. customThe reaction mixture was quenched by addition of methanol
  5. customThe organic layer was evaporated in rotavap
  6. extractionaqueous layer extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customto furnish the crude product
  11. customPurification by flash chromatography (60-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b762fb3a879b4984bbf58d6fee7b127e
Source dataset
uspto-grants-2015_05
Patent number
US09024019B2

Reaction notes

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