Acetonitrile → 3-(5-Fluoro-2-pyridyl)-5-(3-(1-benzyl-1,2,5,6-tetrahydropyridin-3-yl)-5-fluorophenyl)-1,2,4-oxadiazole

HRID 431980Notes

Reaction equation

HRID 431980 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[C:17]([C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH:16]=[C:15]([F:25])[CH:14]=3)[O:10][N:9]=2)=[N:6][CH:7]=1.C(#N)C.[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:14]=[C:15]([F:25])[CH:16]=[C:17]([C:19]4[CH2:20][N:21]([CH2:29][C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:22][CH2:23][CH:24]=4)[CH:18]=3)[O:10][N:9]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7498Benzyl BromideHCID 4311764Sodium borohydrideHCID 101318283-(5-Fluoro-2-pyridyl)-5-(3-fluoro-5-(3-pyridyl)phenyl)-1,2,4-oxadiazole

Product 1

HCID 101135083-(5-Fluoro-2-pyridyl)-5-(3-(1-benzyl-1,2,5,6-tetrahydropyridin-3-yl)-5-fluorophenyl)-1,2,4-oxadiazoleYield 8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a screw cap vial equipped with stir bar added 3-(5-Fluoro-2-pyridyl)-5-(3-fluoro-5-(3-pyridyl)phenyl)-1,2,4-oxadiazole (100 mg, 0.30 mmol), acetonitrile (2 ml) and benzyl bromide (0.05 ml, 0.39 mmol). Stirred the resulting mixture at 90° C. for 4h. Cooled the mixture to room temperature, concentrated in-vacuo and triturated the residue with 30% ethyl acetate in hexanes to isolate the quarternary salt. The isolated solid was dissolved in methanol (2 ml) and treated with sodium borohydride (22.6 mg, 0.60 mmol) at 0° C. The bright yellow reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated in-vacuo and the residue was dissolved in dichloromethane (20 ml). The organic phase was sequentially washed with water (20 ml) and brine (20 ml), dried (sodium sulfate), filtered and concentrated in-vacuo. The crude residue was purified on silica gel using 30% ethyl acetate in hexanes to isolate the title compound (10.1 mg, 8%) as yellow oil. 1H-NMR (CDCl3), δ (ppm): 8.69 (d, 1H), 8.26 (dd, 1H), 8.02 (s, 1H), 7.80 (dd, 1H), 7.60 (dt, 1H), 7.32 (m, 6H), 6.34 (m, 1H), 3.73 (s, 2H), 3.40 (bs, 2H), 2.63 (t, 2H), 2.39 (m, 2H).

Workup

  1. customIn a screw cap vial
  2. customequipped
  3. stirringStirred the resulting mixture at 90° C. for 4h
  4. concentrationconcentrated in-vacuo
  5. customtriturated the residue with 30% ethyl acetate in hexanes
  6. customto isolate the quarternary salt
  7. stirringThe bright yellow reaction mixture was stirred at room temperature for 2 h
  8. concentrationThe reaction mixture was concentrated in-vacuo
  9. dissolutionthe residue was dissolved in dichloromethane (20 ml)
  10. washThe organic phase was sequentially washed with water (20 ml) and brine (20 ml)
  11. dry with materialdried (sodium sulfate)
  12. filtrationfiltered
  13. concentrationconcentrated in-vacuo
  14. customThe crude residue was purified on silica gel using 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-71521f9b79ac45dd9a24ab87e7c22917
Source dataset
uspto-grants-2003_12
Patent number
US06660753B2

Reaction notes

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