Trifluoroacetic acid → 3-(3-(cyclopropanecarboxamido)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoro-methyl)phenyl)benzamide

HRID 876896Notes

Reaction equation

HRID 876896 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[C:15]3[C:10](=[CH:11][C:12]([NH:16][C:17]4[CH:18]=[C:19]([CH:33]=[CH:34][C:35]=4[CH3:36])[C:20]([NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)=[O:21])=[CH:13][CH:14]=3)[N:9](COCC[Si](C)(C)C)[N:8]=2)=[O:5])[CH2:3][CH2:2]1.[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46]>C(Cl)Cl>[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46].[CH:1]1([C:4]([NH:6][C:7]2[C:15]3[C:10](=[CH:11][C:12]([NH:16][C:17]4[CH:18]=[C:19]([CH:33]=[CH:34][C:35]=4[CH3:36])[C:20]([NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:30])[F:32])[CH:24]=4)=[O:21])=[CH:13][CH:14]=3)[NH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674006613-(3-(cyclopropanecarboxamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

Product 2

HCID 6422Trifluoroacetic acidHCID 682341303-(3-(cyclopropanecarboxamido)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoro-methyl)phenyl)benzamideYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(3-(cyclopropanecarboxamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide (25 mg) in CH2Cl2 (1 mL) was added TFA (0.25 mL) at room temperature. The reaction mixture was stirred for 2 hours and the organic solvent was concentrated under reduced pressure. To a solution of the resulting mixture in THF (0.5 mL) and MeOH (0.5 mL) was added LiOH aqueous solution (1.0 M, 1.0 mL). The resulting mixture was stirred for another 2 hours at room temperature. The organic solvent was removed under reduced pressure and the aqueous layer was extracted with ethyl acetate. The organic extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by Prep HPLC and acetonitrile was removed under reduced pressure. The remained water was freeze-dried to afford TFA salt of title compound (16 mg, 66%), MS (ESI) m/z 494 (M+H)+.

Workup

  1. concentrationthe organic solvent was concentrated under reduced pressure
  2. additionTo a solution of the resulting mixture in THF (0.5 mL) and MeOH (0.5 mL) was added LiOH aqueous solution (1.0 M, 1.0 mL)
  3. stirringThe resulting mixture was stirred for another 2 hours at room temperature
  4. customThe organic solvent was removed under reduced pressure
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by Prep HPLC and acetonitrile
  10. customwas removed under reduced pressure
  11. dry with materialThe remained water was freeze-dried

Sources & evidence

ORD record
ord-9baaf77a3f124a35afddd07456819914
Source dataset
uspto-grants-2015_03
Patent number
US08987275B2

Reaction notes

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