Triethylamine → 2-[[4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl]amino]ethyl methanesulfonate

HRID 69818Notes

Reaction equation

HRID 69818 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:19]([NH:20][CH2:21][CH2:22][OH:23])=[N:18][O:17][N:16]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(OCC)(=O)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C>O>[CH3:30][S:31]([O:23][CH2:22][CH2:21][NH:20][C:19]1[C:15]([C:10]2[N:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Br:1])[CH:3]=3)[C:13](=[O:14])[O:12][N:11]=2)=[N:16][O:17][N:18]=1)(=[O:33])=[O:32]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 666056584-(3-Bromo-4-fluorophenyl)-3-(4-((2-hydroxyethyl)amino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 866379982-[[4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl]amino]ethyl methanesulfonateYield 97.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-(3-bromo-4-fluorophenyl)-3-(4-(2-hydroxyethylamino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one (72.2 g, 0.188 mol) was mixed with ethyl acetate (600 mL). Methanesulfonyl chloride (19.2 mL, 0.248 mol) was added followed by triethylamine (34.9 mL, 0.250 mol). The reaction was stirred at room temperature for 5 min. When LCMS indicated completion of reaction (M+H=442), 500 mL of water was added into reaction. The reaction was extracted with ethyl acetate (2×500 mL). The combined ethyl acetate solution was washed with brine (500 mL), dried over sodium sulfate and concentrated to give 85.1 g crude brown solid. 1H NMR verified the structure. Crude yield was 97%. LCMS for C13H11BrFN5O6SNa (M+Na)+: m/z=485.9, 487.9. 1H NMR (400 MHz, DMSO-d6): δ 8.08 (dd, J=6.2, 2.5 Hz, 1 H), 7.72 (m, 1 H), 7.58 (t, J=8.7 Hz, 1 H), 6.75 (t, J=5.9 Hz, 1 H), 4.36 (t, J=5.3 Hz, 2 H), 3.58 (dd, J=11.2, 5.6 Hz, 2 H), 3.18 (s, 3 H).

Workup

  1. additionwas added into reaction
  2. extractionThe reaction was extracted with ethyl acetate (2×500 mL)
  3. washThe combined ethyl acetate solution was washed with brine (500 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3a4a49d892334d26885a7cb57131c386
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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