Trifluoroacetic acid → (S)-N-(1-(3-(4 chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

HRID 2170395Notes

Reaction equation

HRID 2170395 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C@@H:17]([NH:27]C(=O)OC(C)(C)C)[CH2:18][C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)=[N:13][CH:14]=[CH:15][CH:16]=2)=[C:7]2[C:3]=1[C:4]([NH:36][S:37]([CH3:40])(=[O:39])=[O:38])=[N:5][N:6]2[CH3:35].[F:41][C:42]([F:47])([F:46])[C:43](O)=[O:44].FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C@@H:17]([NH:27][C:43](=[O:44])[C:42]([F:47])([F:46])[F:41])[CH2:18][C:19]3[CH:20]=[C:21]([F:26])[CH:22]=[C:23]([F:25])[CH:24]=3)=[N:13][CH:14]=[CH:15][CH:16]=2)=[C:7]2[C:3]=1[C:4]([NH:36][S:37]([CH3:40])(=[O:38])=[O:39])=[N:5][N:6]2[CH3:35]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 90290217(S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Product 1

HCID 90281453(S)-N-(1-(3-(4 chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate (57A, 3.39 g, 5.73 mmol) in DCM (5 mL) was added trifluoroacetic acid (5 mL). The reaction mixture was stirred at room temperature for 2.5 hours. Upon complete removal of the Boc protecting group, trifluoroacetic anhydride (2.02 mL, 14.31 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes. Upon completion, the reaction mixture was filtered through celite, concentrated in vacuo, taken in EtOAc, and carefully neutralized with 1M aqueous NaHCO3 until the aqueous layer was at pH 10. The organic layer was collected and the aqueous layer extracted once more with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column chromatography, eluting with 0-100% EtOAc in hexanes to give the title compound. MS (m/z) 588.14 [M+H]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  3. filtrationUpon completion, the reaction mixture was filtered through celite
  4. concentrationconcentrated in vacuo
  5. customThe organic layer was collected
  6. extractionthe aqueous layer extracted once more with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel column chromatography
  11. washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-d686f97c8c8d4245a5550ac12a9d698e
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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