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 2402203Notes

Reaction equation

HRID 2402203 reaction equation
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][S:15]([NH:18][CH2:19][CH2:20][NH:21][C:22]1[C:26]([C:27]2[N:31]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([Br:39])[CH:33]=3)[C:30](=[O:40])[O:29][N:28]=2)=[N:25][O:24][N:23]=1)(=[O:17])=[O:16])(C)(C)C>O>[Br:39][C:34]1[CH:33]=[C:32]([N:31]2[C:30](=[O:40])[O:29][N:28]=[C:27]2[C:26]2[C:22]([NH:21][CH2:20][CH2:19][NH:18][S:15]([NH2:14])(=[O:16])=[O:17])=[N:23][O:24][N:25]=2)[CH:37]=[CH:36][C:35]=1[F:38]

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, 1H), 7.72 (m, 1H), 7.59 (t, J=8.7 Hz, 1H), 6.67 (t, J=5.9 Hz, 1H), 6.52 (t, J=6.0 Hz, 1H), 3.38 (dd, J=12.7, 6.3 Hz, 2H), 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-600f9b3d2a4546198f7c5b959d24f47f
Source dataset
uspto-grants-2014_08
Patent number
US08796319B2

Reaction notes

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