Trifluoroacetic acid → N-(5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)acetamide

HRID 2203433Notes

Reaction equation

HRID 2203433 reaction equation
[C:1]([N:4]([C:12]1[C:16]2[CH:17]=[C:18]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=3[O:28][C:29]3[CH:34]=[C:33]([F:35])[C:32]([S:36](=[O:55])(=[O:54])[N:37](CC4C=CC(OC)=CC=4OC)[C:38]4[S:42][N:41]=[CH:40][N:39]=4)=[CH:31][C:30]=3[F:56])[CH:19]=[CH:20][C:15]=2[O:14][N:13]=1)C(=O)OC(C)(C)C)(=[O:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[S:42]1[C:38]([NH:37][S:36]([C:32]2[C:33]([F:35])=[CH:34][C:29]([O:28][C:22]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:21]=3[C:18]3[CH:19]=[CH:20][C:15]4[O:14][N:13]=[C:12]([NH:4][C:1](=[O:3])[CH3:2])[C:16]=4[CH:17]=3)=[C:30]([F:56])[CH:31]=2)(=[O:54])=[O:55])=[N:39][CH:40]=[N:41]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90389189tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate

Product 1

HCID 71558163N-(5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)acetamideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate (0.21 g, 0.25 mmol) in dichloromethane (20 mL) at 0° C., under nitrogen, was treated with trifluoroacetic acid (75 μL, 0.8 mmol) and stirred for 1 h. The reaction mixture was allowed to warm to ambient temperature, stirred for 3 h and concentrated in vacuo. The residue was purified by reverse phase HPLC to afford N-(5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)acetamide as a colorless solid in 35% yield (0.05 g): 1H NMR (300 MHz, DMSO-d6) δ 11.05 (s, 1H), 8.47 (s, 1H), 8.11 (s, 1H), 7.76-7.63 (m, 3H), 7.59, (d, J=2.3 Hz, 1H), 7.49 (dd, J=9.1, 2.7 Hz, 1H), 7.27 (d, J=8.8 Hz, 1H), 7.13 (dd, J=10.3, 6.5 Hz, 1H), 2.12 (s, 3H), (Note: sulfonamide N—H not observed); MS (ES+) m/z 599.6 (M+23), 601.6 (M+23).

Workup

  1. stirringstirred for 3 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7907c56876a241c69d122efe3fb7f92b
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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