Trifluoroacetic acid → Nav1.7-IN-8

HRID 2203432Notes

Reaction equation

HRID 2203432 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][C:33]2[CH:38]=[C:37]([F:39])[C:36]([S:40](=[O:59])(=[O:58])[N:41](CC3C=CC(OC)=CC=3OC)[C:42]3[S:46][N:45]=[CH:44][N:43]=3)=[CH:35][C:34]=2[F:60])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][N:14]=[C:13]([N:16](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:12]=3[CH:31]=2)[CH:7]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:16][C:13]1[C:12]2[CH:31]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:32][C:33]3[C:34]([F:60])=[CH:35][C:36]([S:40]([NH:41][C:42]4[S:46][N:45]=[CH:44][N:43]=4)(=[O:58])=[O:59])=[C:37]([F:39])[CH:38]=3)[CH:9]=[CH:10][C:11]=2[O:15][N:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 123740120Di-tert-butyl [5-(5-chloro-2-{4-[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)sulfamoyl]-2,5-difluorophenoxy}phenyl)-1,2-benzoxazol-3-yl]imidodicarbonate

Product 1

HCID 71559365Nav1.7-IN-8Yield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of di-tert-butyl [5-(5-chloro-2-{4-[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)sulfamoyl]-2,5-difluorophenoxy}phenyl)-1,2-benzoxazol-3-yl]imidodicarbonate (1.70 g, 1.92 mmol) in dichloromethane (25 mL) was added trifluoroacetic acid (10 mL). The reaction mixture was stirred at ambient temperature for 4 h and concentrated in vacuo. The residue was taken up in methanol (15 mL) and filtered. The filtrate was concentrated in vacuo and triturated with dichloromethane/diethyl ether (2:1 v/v, 15 mL) to afford 4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a colorless solid in 63% yield (0.65 g): 1H NMR (300 MHz, DMSO-d6) δ8.49 (s, 1H), 7.95 (s, 1H), 7.72-7.66 (m, 1H), 7.62-7.59 (m, 2H), 7.49-7.42 (m, 2H), 7.26-7.24 (d, J=8.4 Hz, 1H), 7.14-7.08 (m, 1H), 6.47-6.40 (br s, 2H); MS (ES+) m/z 535.8 (M+1), 537.8 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated in vacuo
  4. customtriturated with dichloromethane/diethyl ether (2:1 v/v, 15 mL)

Sources & evidence

ORD record
ord-695cea75176b40a1b8af6ad9d7291a26
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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