Acetamide → N-(3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-oxadiazol-5-yl)acetamide

HRID 634288Notes

Reaction equation

HRID 634288 reaction equation
[C:1]([NH2:4])(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[I:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]3[N:29]=[C:28](C(Cl)(Cl)Cl)[O:27][N:26]=3)[CH:23]=2)[N:18]([S:34]([C:37]2[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=2)(=[O:36])=[O:35])[CH:17]=1>C1COCC1>[I:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]3[N:29]=[C:28]([NH:4][C:1](=[O:3])[CH3:2])[O:27][N:26]=3)[CH:23]=2)[N:18]([S:34]([C:37]2[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=2)(=[O:35])=[O:36])[CH:17]=1

Participants

5

Reactant 3

HCID 178AcetamideHCID 2733832Lithium HexamethyldisilazideHCID 683286363-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(trichloromethyl)-1,2,4-oxadiazole

Product 1

HCID 68328892N-(3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-oxadiazol-5-yl)acetamideYield 55.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of acetamide (91.5 mg, 1.54 mmol in dry THF (10 mL) was added 1.0M lithium bis(trimethylsilyl)amide (LHMDS) (1.2 mL, 1.54 mmol) at −78° C. and the mixture was stirred for 45 min at −78° C. and 10 min at −10° C. Again the reaction was cooled back to −78° C. To the mixture at −78° C. was added 3-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(trichloromethyl)-1,2,4-oxadiazole (600 mg, 1.03 mmol) and the reaction was stirred at RT for 12 h. The solvent was then removed in vacuo and the residue was diluted with water (10 mL) and extracted with EtOAc (2×20 mL). The combined organic layers were dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified with basic alumina column chromatography (eluent: 35% EtOAc in petroleum ether) to give N-(3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-oxadiazol-5-yl)acetamide (300 mg, 55.5%) as an off brown solid. MS (ESI, pos. ion) m/z: 523.0 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 12.22 (brs, 1H), 8.22 (s, 1H), 8.15 (d, J=8.8 Hz, 1H), 8.02-7.90 (m, 4H), 7.44 (d, J=8.0 Hz, 2H), 2.33 (m, 3H), 2.19 (s, 3H).

Workup

  1. temperatureAgain the reaction was cooled back to −78° C
  2. stirringthe reaction was stirred at RT for 12 h
  3. customThe solvent was then removed in vacuo
  4. additionthe residue was diluted with water (10 mL)
  5. extractionextracted with EtOAc (2×20 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified with basic alumina column chromatography (eluent: 35% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-ad3e932df2c44b04b8d509da7b1c00f6
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…