Trifluoroacetic acid → 1-(2-(2-(5-Methyl-2-((6-(piperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592441Notes

Reaction equation

HRID 592441 reaction equation
[C:1]([C:4]1([C:7]2[CH:41]=[CH:40][CH:39]=[CH:38][C:8]=2[CH2:9][CH2:10][C:11]2[C:16]([CH3:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([CH:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]4)=[N:23][CH:24]=3)[N:12]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[CH3:17][C:16]1[C:11]([CH2:10][CH2:9][C:8]2[CH:38]=[CH:39][CH:40]=[CH:41][C:7]=2[C:4]2([C:1]([NH2:2])=[O:3])[CH2:6][CH2:5]2)=[N:12][C:13]([NH:18][C:19]2[CH:24]=[N:23][C:22]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[CH:21][CH:20]=2)=[N:14][CH:15]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 86712319tert-Butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 867123201-(2-(2-(5-Methyl-2-((6-(piperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate A45 (0.200 g, 0.359 mmol) in DCM (10 mL) was treated with TFA (0.41 mL, 5.4 mmol) and stirred at room temperature for 4 hours. An extra aliquot of TFA (0.14 mL, 1.8 mmol) was added to the reaction mixture and stirring was continued for 1 hour at room temperature. Sat. aq. NaHCO3 (˜20 mL) was carefully added to the mixture followed by aq. NaOH (2 M, ˜20 mL). DCM was removed in vacuo and the aqueous mixture was extracted with EtOAc (3×30 mL). The organic extracts were combined, washed with brine, dried (MgSO4) and the solvent removed in vacuo. The residue was dissolved in DCM before cyclohexane was added to form a white precipitate. The suspension was sonicated for 10 minutes and filtered to give the title compound A46 as a white solid (0.129 g, 79%). LCMS-D: rt 3.08 min; m/z 457 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 1 hour at room temperature
  3. customDCM was removed in vacuo
  4. extractionthe aqueous mixture was extracted with EtOAc (3×30 mL)
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. dissolutionThe residue was dissolved in DCM before cyclohexane
  9. additionwas added
  10. customto form a white precipitate
  11. customThe suspension was sonicated for 10 minutes
  12. filtrationfiltered

Sources & evidence

ORD record
ord-11e276672ddf420384e58b40a9ba1467
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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