Iodine → 5-(3-iodo-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

HRID 634089Notes

Reaction equation

HRID 634089 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[O:14][C:13]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)=[N:12][N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[I:25]I.[OH-].[K+].S(=O)(O)[O-].[Na+]>CN(C=O)C>[I:25][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:10]3[O:14][C:13]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)=[N:12][N:11]=3)[CH:5]=2)[NH:1][CH:2]=1

Participants

6

Reactant 4

HCID 807IodineHCID 14797Potassium HydroxideHCID 23665763Sodium BisulfiteHCID 867250885-(1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 867250895-(3-iodo-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amineYield 59.44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (28.0 g, 87.5 mmol) in DMF (270 mL) was added I2 (24.42 g, 96.25 mmol) followed by KOH (12.27 g, 218.75 mmol). The mixture was stirred at RT for 1 h, then poured into ice with 5% sodium bisulfite. The aqueous layer was extracted with DCM and the combined organic layers were washed with water, dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 2-3% MeOH in DCM) to give 5-(3-iodo-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (23.2 g, 52.0 mmol, 59.44%). MS (ESI, pos. ion) m/z: 447.0 (M+1); 1H-NMR (DMSO-d6) δ 11.87 (s, 1H), 8.22 (t, 1H), 7.69-7.65 (m, 2H), 7.44 (d, J=9 Hz, 2H), 7.34 (s, 1H), 6.92 (d, J=9 Hz, 2H), 5.76 (s, 1H), 4.38 (d, 2H), 3.73 (s, 3H).

Workup

  1. extractionThe aqueous layer was extracted with DCM
  2. washthe combined organic layers were washed with water
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 2-3% MeOH in DCM)

Sources & evidence

ORD record
ord-f3d54a0fd54b4c969698894632d7f615
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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