Water → 3-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(trichloromethyl)-1,2,4-oxadiazole

HRID 634275Notes

Reaction equation

HRID 634275 reaction equation
[OH:1][N:2]=[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([S:14]([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH:9]=[C:8]2[I:24])[NH2:4].CCN(CC)CC.[Cl:32][C:33]([Cl:38])([Cl:37])[C:34](Cl)=O.O>C1COCC1>[I:24][C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[C:5]([C:3]3[N:4]=[C:34]([C:33]([Cl:38])([Cl:37])[Cl:32])[O:1][N:2]=3)[CH:6]=2)[N:10]([S:14]([C:17]2[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6420Trichloroacetyl chlorideHCID 8471TriethylamineHCID 86725116N'-hydroxy-3-iodo-1-tosyl-1H-indole-5-carboximidamide

Product 1

HCID 683286363-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(trichloromethyl)-1,2,4-oxadiazoleYield 20.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N′-hydroxy-3-iodo-1-tosyl-1H-indole-5-carboximidamide (950 mg, 2.09 mmol) in dry THF (10 mL) was added Et3N (1.4 mL, 10.10 mmol) and O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate (HBTU) (1.6 g, 4.18 mmol) at 0° C. Trichloroacetyl chloride (0.48 mL, 2.51 mmol) was added portion wise at 0° C. and the reaction was stirred for 16 h at RT. The mixture was treated with H2O (10 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was further with basic alumina chromatography (eluent: 5% EtOAc in petroleum ether) to afford 3-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(trichloromethyl)-1,2,4-oxadiazole (250 mg, 20.8%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.26 (s, 1H), 8.21 (d, J=8.8 z, 1H), 8.10 (t, J=1.2 Hz, 1H), 7.99-7.95 (m, 3H), 7.44 (d, J=8.4 Hz, 1H), 2.32 (s, 3H).

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fe8a9e89433b4cd8a05d39668de7ae67
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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