Trifluoroacetic acid → tert-Butyl 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)sulfamoylcarbamate

HRID 632538Notes

Reaction equation

HRID 632538 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.CO[CH:23](OC)[CH2:24][NH:25][S:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:28])=[O:27].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[Br:19][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:20])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][CH2:23][CH2:24][NH:25][S:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:27])=[O:28])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][C:15]=1[F:18]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 591483883-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-oneHCID 118059919HCID 118059919, compound

Product 1

HCID 68052882tert-Butyl 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)sulfamoylcarbamateYield 29.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (103 mg, 0.302 mmol, 1.5 equiv.; Step D) and tert-butyl N-(2,2-dimethoxyethyl)sulfamoylcarbamate (57.2 mg, 0.201 mmol) in dichloromethane (1.0 mL) was stirred under N2 at room temperature. To this mixture was added trifluoroacetic acid (0.50 mL, 6.5 mmol) and triethylsilane (80.2 μL, 0.502 mmol, 2.5 equiv.) drop-wise. This reaction mixture was stirred at room temperature for 2 h. HPLC indicated approximately 30% conversion. The reaction mixture was cooled to 0° C. and quenched with saturated sodium bicarbonate to pH ˜8. The mixture was extracted in ethyl acetate (3×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by preparative TLC (50% ethyl acetate/hexane) to give the desired product (27.5 mg, 29.5%) as an off-white solid. 1H NMR (DMSO-d6, 400 MHz): δ 10.90 (s, 1H), 8.08 (dd, J=6.2, 2.5 Hz, 1H), 7.72 (m, 1H), 7.59 (t, J=8.6 Hz, 1H), 6.58 (t, J=5.7 Hz, 1H), 3.38 (dd, J=12.7, 6.2 Hz, 2H), 3.10 (dd, J=12.1, 5.9 Hz, 2H), 1.41 (s, 9H). C17H19BrFN7O7S (MW 564.34), LCMS (EI) m/e 485.8/487.8 (M+-C5H8O2+Na).

Workup

  1. stirringThis reaction mixture was stirred at room temperature for 2 h
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with saturated sodium bicarbonate to pH ˜8
  4. extractionThe mixture was extracted in ethyl acetate (3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by preparative TLC (50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f6b6f1bf6b214920858cd6ecf4674559
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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