Sodium Iodide → 3-(4-((2-Aminoethyl)amino)-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydroiodide

HRID 415864Notes

Reaction equation

HRID 415864 reaction equation
[N:1]([CH2:4][CH2:5][NH:6][C:7]1[C:8]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([Br:24])[CH:18]=3)[C:15](=[O:25])[O:14][N:13]=2)=[N:9][O:10][N:11]=1)=[N+]=[N-].[I-:26].[Na+].Cl[Si](C)(C)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>CO.O>[IH:26].[NH2:1][CH2:4][CH2:5][NH:6][C:7]1[C:8]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([Br:24])[CH:18]=3)[C:15](=[O:25])[O:14][N:13]=2)=[N:9][O:10][N:11]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 24477Sodium ThiosulfateHCID 86637999HCID 86637999, compound

Product 1

HCID 666057413-(4-((2-Aminoethyl)amino)-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydroiodideYield 95.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

3-(4-(2-azidoethylamino)-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (80.0 g, 0.194 mol) was mixed with methanol (800 mL). Sodium iodide (175.0 g, 1.17 mol) was added. The reaction was stirred at room temperature for 10 min. Chlorotrimethylsilane (148 mL, 1.17 mol) was dissolved in methanol (100 mL) and added to the reaction over 30 min. The reaction temperature rose 42° C. The reaction was stirred at room temperature for 30 min. LCMS indicated reaction completed (M+H=386). The reaction was quenched with sodium thiosulfate (190.0 g, 1.20 mol) in water (900 mL). A large amount of solid precipitated. The product was collected by filtration (filtration speed was slow), rinsed with water (200 mL), and dried on vacuum overnight. The filter cake was slurried in ethyl acetate (500 mL) for 30 min. The product was filtered (filtration speed is slow) and dried under vacuum over weekend to give 95 g of an off-white solid. LCMS for C12H11BrFN6O3 (M+H)+: m/z=384.9, 386.9. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (m, 4H), 7.76 (m, 1H), 7.58 (t, J=8.7 Hz, 1H), 6.78 (t, J=6.1 Hz, 1H), 3.51 (dd, J=11.8, 6.1 Hz, 2H), 3.02 (m, 2H).

Workup

  1. additionadded to the reaction over 30 min
  2. customrose 42° C
  3. stirringThe reaction was stirred at room temperature for 30 min
  4. customreaction
  5. customA large amount of solid precipitated
  6. filtrationThe product was collected by filtration (filtration speed was slow)
  7. washrinsed with water (200 mL)
  8. customdried on vacuum overnight
  9. waitThe filter cake was slurried in ethyl acetate (500 mL) for 30 min
  10. filtrationThe product was filtered
  11. filtration(filtration speed is slow)
  12. customdried under vacuum over weekend

Sources & evidence

ORD record
ord-d58a3aeac8e24d3685cedecabf2fe685
Source dataset
uspto-grants-2012_01
Patent number
US08088803B2

Reaction notes

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