Sodium Thiosulfate → 2-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409551Notes

Reaction equation

HRID 2409551 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[CH:18][N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1C(=O)N([I:26])C(=O)C1.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([I:26])[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 120273N-Iodosuccinimide3×HCID 667170372-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 667169462-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazoleYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazole (from the previous step, 0.65 g, 2.50 mmol, 1 eq) was dissolved in DMF (9 mL), and NIS (0.41 g, 1.75 mmol, 0.7 eq) was added. The mixture was stirred at RT in an argon atmosphere. After 2 hours HPLC-MS analysis indicated incomplete conversion; 0.1 g of NIS was added, and the reaction mixture was stirred at RT overnight. Another 0.08 g of NIS was added, and after another 2 h of stirring at RT the reaction mixture was poured into 20 mL of aq. sodium thiosulfate (10%) and extracted with EtOAc. The combined organic layers were washed with water, dried (Na2SO4) and concentrated, and the residue (0.888 g) was purified by column chromatography (SiO2, cyclohexane/20-100% EtOAc) to afford the desired product (white solid, 0.336 g, 36% yield, 2 steps). HPLC-MS: (10-95% B in 4 min, 0.5 mL/min+2 min 100% B, 0.7 mL/min): tR=4.42 min, [M+H]+ m/z 387.9; 1H NMR (300 MHz, DMSO) δ/ppm 7.50 (dd, J=2.2, 8.4, 1H), 7.42 (d, J=2.1, 1H), 7.37 (s, 1H), 7.16 (d, J=8.5, 1H), 3.89 (s, 3H), 3.86 (s, 3H).

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. stirringafter another 2 h of stirring at RT the reaction mixture
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customthe residue (0.888 g) was purified by column chromatography (SiO2, cyclohexane/20-100% EtOAc)

Sources & evidence

ORD record
ord-f4faa40e7eda433eb692ed70f73b6e72
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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