Hydrochloric Acid → HCID 178514784, compound

HRID 69765Notes

Reaction equation

HRID 69765 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2C(=O)[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: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.[OH-].[Na+].Cl>C1COCC1>[NH2:27][S:24]([NH:23][CH2:22][CH2:21][NH:20][C:16]1[C:15]([C:10](=[N:11][OH:12])[NH:9][C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Br:1])[CH:3]=2)=[N:19][O:18][N:17]=1)(=[O:25])=[O:26]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 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]sulfamide

Product 1

HCID 178514784HCID 178514784, compoundYield 336.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a crude mixture of 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 (2.4 mol) containing residual amounts of trifluoroacetic acid stirring in a 22 L flask was added THF (5 L). The resulting solution was cooled to 0° C. using an ice bath and 2 N NaOH (4 L) was added at a rate so that the temperature did not exceed 10° C. After stirring at ambient temperature for 3 h (LCMS indicated no starting material remained), the pH was adjusted to 3-4 with concentrated HCl (˜500 mL). The THF was removed in vacuo, and the resulting mixture was extracted with ethyl acetate (15 L). The organic layer was washed with water (5 L), brine (5 L), and the solvents removed in vacuo to afford a solid. The solid was triturated with MTBE (2×2 L), combined with three other reactions of the same size, and dried overnight in a convection oven to afford a white solid (3535 g). The solid was recrystallized (3×22 L flasks, 2:1 water:ethanol, 14.1 L each flask) and dried in a 50° C. convection oven to a constant weight to furnish the title compound as an off-white solid (3290 g, 78%). LCMS for C11H14BrFN7O4S (M+H)+: m/z=437.9, 439.9. 1HNMR (400 MHz, DMSO-d6): δ 11.51 (s, 1 H), 8.90 (s, 1 H), 7.17 (t, J=8.8 Hz, 1 H), 7.11 (dd, J=6.1, 2.7 Hz, 1 H), 6.76 (m, 1 H), 6.71 (t, J=6.0 Hz, 1H), 6.59 (s, 2 H), 6.23 (t, J=6.1 Hz, 1 H), 3.35 (dd, J=10.9, 7.0 Hz, 2 H), 3.10 (dd, J=12.1, 6.2 Hz, 2 H).

Workup

  1. customdid not exceed 10° C
  2. customThe THF was removed in vacuo
  3. extractionthe resulting mixture was extracted with ethyl acetate (15 L)
  4. washThe organic layer was washed with water (5 L), brine (5 L)
  5. customthe solvents removed in vacuo
  6. customto afford a solid
  7. customThe solid was triturated with MTBE (2×2 L)
  8. customdried overnight in a convection oven

Sources & evidence

ORD record
ord-434ec10fc8d04869bc2bfca09813adad
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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