Trifluoroacetic acid → N-[2-({4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide

HRID 632534Notes

Reaction equation

HRID 632534 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:16]([NH:20][CH2:21][CH2:22][N:23](CC3C=CC(OC)=CC=3)[S:24]([N:27](CC3C=CC(OC)=CC=3)C(=O)OC(C)(C)C)(=[O:26])=[O:25])=[N:17][O:18][N:19]=2)[CH:5]=[CH:6][C:7]=1[F:8].FC(F)(F)C(O)=O>>[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:16]([NH:20][CH2:21][CH2:22][NH:23][S:24]([NH2:27])(=[O:25])=[O:26])=[N:17][O:18][N:19]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118069749HCID 118069749, compound

Product 1

HCID 66605130N-[2-({4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamideYield 87%

Conditions

Temperature
70 °C

Procedure

To a 25-mL flask was added tert-butyl {[[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl](4-methoxybenzyl)amino]sulfonyl}(4-methoxybenzyl)carbamate (40.2 mg, 0.050 mmol) in trifluoroacetic acid (TFA, 0.50 mL, 6.5 mmol) at ambient temperature. This reaction mixture was heated to 70° C. under N2 and stirred for 1 h. HPLC indicated reaction completed. The reaction mixture was cooled to room temperature and the TFA was evaporated. The residual TFA was removed by treatment with dichloromethane (3×10 mL) followed by evaporation in vacuum. The residue was then triturated with dichloromethane and methanol to give the desired product (20 mg, 87%) as a crude off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.08 (dd, J=6.2, 2.5 Hz, 1 H), 7.72 (m, 1 H), 7.59 (t, J=8.7 Hz, 1 H), 6.67 (t, J=5.9 Hz, 1H), 6.55 (s, 2H) 6.52 (t, J=6.0 Hz, 1 H), 3.38 (dd, J=12.7, 6.3 Hz, 2 H), 3.11 (dd, J=12.3, 6.3 Hz, 2H); C12H11BrFN7O5S (MW 464.23), LCMS (EI) m/e 487.8/489.8 (M++Na).

Workup

  1. customreaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe TFA was evaporated
  4. customThe residual TFA was removed by treatment with dichloromethane (3×10 mL)
  5. customfollowed by evaporation in vacuum
  6. customThe residue was then triturated with dichloromethane and methanol

Sources & evidence

ORD record
ord-75a9430fd2514751ae366036b7d5f69d
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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