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

Temperature

-10 °C

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).

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)

ORD record

ord-ad3e932df2c44b04b8d509da7b1c00f6

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321756B2