Trifluoroacetic acid → N-[1-{[3-(Aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

HRID 1874695Notes

Reaction equation

HRID 1874695 reaction equation
CC([N:5]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([O:27][CH3:28])[C:22]([F:26])=[CH:23][CH:24]=3)[C:19]([NH:29][S:30]([C:33]3[S:34][C:35]([Cl:38])=[CH:36][CH:37]=3)(=[O:32])=[O:31])=[N:18]2)[CH:11]=1)C(=O)[O-])(C)C.FC(F)(F)C(O)=O>ClCCl.CO.CS(C)=O>[NH2:5][CH2:9][C:10]1[CH:11]=[C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([O:27][CH3:28])[C:22]([F:26])=[CH:23][CH:24]=3)[C:19]([NH:29][S:30]([C:33]3[S:34][C:35]([Cl:38])=[CH:36][CH:37]=3)(=[O:32])=[O:31])=[N:18]2)[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86644812HCID 86644812, compound

Product 1

HCID 59455989N-[1-{[3-(Aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamideYield 45%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

1,1-Dimethylethyl[(3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-5-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]carbamate (for a preparation see Intermediate 60) (2.7 g, 4.65 mmol) was dissolved in dichloromethane (20 mL). Trifluoroacetic acid (5.00 mL) was added to the reaction and stirred for 1 h. The reaction mixture was concentrated in vacuo to leave a purple residue. The residue was dissolved in methanol and loaded onto a methanol pre-conditioned SCX-2 ion-exchange cartridge (70 g). The cartridge was washed well with methanol, followed by HCl in methanol, then methanol and finally ammonia in methanol. Fractions were combined and evaporated in vacuo to give an off white solid, which was dissolved in DMSO, filtered and loaded onto a methanol pre-conditioned SCX-2 ion-exchange cartridge (70 g). The cartridge was washed well with Methanol followed by 2M ammonia in methanol. Evaporation of the solvent from the ammoniacal fractions gave the title compound (1 g, 45%) as a white solid: LCMS (System A) RT=0.84 min, ES+ve m/z 481/483 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto leave a purple residue
  3. washThe cartridge was washed well with methanol
  4. customevaporated in vacuo
  5. customto give an off white solid, which
  6. filtrationfiltered
  7. washThe cartridge was washed well with Methanol
  8. customEvaporation of the solvent from the ammoniacal fractions

Sources & evidence

ORD record
ord-605a6414c1834d559fb7e8e46701b247
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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