Trifluoroacetic acid → 1-(4-(Cyanomethyl)-1-(2-fluoroethyl)piperidin-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide

HRID 521230Notes

Reaction equation

HRID 521230 reaction equation
[F:1][CH2:2][CH2:3]O.FC(F)(F)C([O-])=O.[C:12]([C:15]1[C:16]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[N:17][N:18]([C:20]2([CH2:26][C:27]#[N:28])[CH2:25][CH2:24][NH2+:23][CH2:22][CH2:21]2)[CH:19]=1)(=[O:14])[NH2:13].C(O)(C(F)(F)F)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CN(C=O)C>[C:27]([CH2:26][C:20]1([N:18]2[CH:19]=[C:15]([C:12]([NH2:13])=[O:14])[C:16]([NH:29][C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)=[N:17]2)[CH2:25][CH2:24][N:23]([CH2:3][CH2:2][F:1])[CH2:22][CH2:21]1)#[N:28]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 97372-FluoroethanolHCID 5049666Sodium triacetoxyborohydrideHCID 867294014-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate2×

Product 1

HCID 867294001-(4-(Cyanomethyl)-1-(2-fluoroethyl)piperidin-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a sealed vial was added 2-fluoroethanol (0.0090 g, 0.14 mmol), PS-IBX (0.28 g, 0.28 mmol, 1.0 mmol/g) suspended in DCE (1.0 mL). The vial was capped and shaken at RT for 16 hours. The reaction was passed though a syringe filter and the eluent was collected into a reaction vial. To the reaction vial was added 4-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate (Intermediate #38-5) (0.020 g, 0.058 mmol), TFA (0.020 mL, 0.26 mmol), Na(OAc)3BH (0.037 g, 0.18 mmol) suspended in DMF (0.50 mL). The reaction vial was capped and heated to 50° C. for 4 hours. The completed reaction was concentrated in vacuo and the residue taken up in DMF (1.0 mL). The crude reaction was passed through a syringe filter and the eluent was directly purified by reverse phase preparative HPLC (using a gradient elution of 0-95% ACN/water with 0.1% v/v TFA modifier). The collected HPLC fraction was concentrated in vacuo and the residue was taken up in MeOH and passed through a Si-Carbonate SPE cartridge. The eluent was collected and evaporated to afford the title compound.

Workup

  1. customThe vial was capped
  2. customThe reaction was passed though a syringe
  3. filtrationfilter
  4. customthe eluent was collected into a reaction vial
  5. customThe reaction vial was capped
  6. temperatureheated to 50° C. for 4 hours
  7. customThe completed reaction
  8. concentrationwas concentrated in vacuo
  9. customThe crude reaction
  10. customwas passed through a syringe
  11. filtrationfilter
  12. customthe eluent was directly purified by reverse phase preparative HPLC (
  13. washa gradient elution of 0-95% ACN/water with 0.1% v/v TFA modifier)
  14. concentrationThe collected HPLC fraction was concentrated in vacuo
  15. customThe eluent was collected
  16. customevaporated

Sources & evidence

ORD record
ord-0c0e875fd38c4affab56e0bf1cf6bd62
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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