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 69764Notes

Reaction equation

HRID 69764 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:10]=[C:11]([N:16]2[C:20](=[O:21])[O:19][N:18]=[C:17]2[C:22]2[C:23]([NH:27][CH2:28][CH2:29][NH:30][S:31]([NH:34]C(=O)OC(C)(C)C)(=[O:33])=[O:32])=[N:24][O:25][N:26]=2)[CH:12]=[CH:13][C:14]=1[F:15]>O>[Br:8][C:9]1[CH:10]=[C:11]([N:16]2[C:20](=[O:21])[O:19][N:18]=[C:17]2[C:22]2[C:23]([NH:27][CH2:28][CH2:29][NH:30][S:31]([NH2:34])(=[O:32])=[O:33])=[N:24][O:25][N:26]=2)[CH:12]=[CH:13][C:14]=1[F:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 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)sulfamoylcarbamate

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]sulfamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 22 L flask containing 98:2 trifluoroacetic acid:water (8.9 L) 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]amino}sulfonyl)carbamate (1931 g, 3.42 mol) in portions over 10 minutes. The resulting mixture was stirred at room temperature for 1.5 h, the solvents removed in vacuo, and chased with dichloromethane (2 L). The resulting solid was treated a second time with fresh 98:2 trifluoroacetic acid:water (8.9 L), heated for 1 h at 40-50° C., the solvents removed in vacuo, and chased with dichloromethane (3×2 L). The resulting white solid was dried in a vacuum drying oven at 50° C. overnight. A total of 5409 g was processed in this manner (4990 g, quant. yield). LCMS for C12H12BrFN7O5S (M+H)+: m/z=463.9, 465.9. 1H NMR (400 MHz, DMSO-d6): δ 8.08 (dd, J=6.2, 2.5 Hz, 1 H), 7.72 (m, 1 H), 7.59 (t, J=8.7 Hz, 1 H), 6.67 (t, J=5.9 Hz, 1 H), 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).

Workup

  1. customthe solvents removed in vacuo
  2. additionThe resulting solid was treated a second time with fresh 98:2 trifluoroacetic acid
  3. temperaturewater (8.9 L), heated for 1 h at 40-50° C.
  4. customthe solvents removed in vacuo
  5. customThe resulting white solid was dried in a vacuum
  6. customdrying oven at 50° C. overnight

Sources & evidence

ORD record
ord-7b750a284c114dcf8109570cbe62dfc4
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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