Trifluoroacetic acid → HCID 57950616, compound

HRID 598888Notes

Reaction equation

HRID 598888 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:27]C(=O)OC(C)(C)C)[CH2:10][CH2:11][N:12]2[CH:16]=[C:15]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[NH:22]C(=O)C4)[CH:14]=[N:13]2)=[CH:4][CH:3]=1.[C:35]([OH:41])(C(F)(F)F)=[O:36]>C(Cl)Cl>[NH2:27][C@@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:10][CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:25]=[CH:24][C:23]3[NH:22][C:35](=[O:36])[O:41][C:19]=3[CH:18]=2)[CH:14]=[N:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86635699HCID 86635699, compound

Product 1

HCID 57950616HCID 57950616, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl(S)-1-(4-chlorophenyl)-4-(4-(2-oxoindolin-5-yl)-1H-pyrazol-1-yl)butan-2-ylcarbamate was dissolved in DCM (2 mL), TFA (2 mL, 26 mmol) was added, and the mixture was stirred for 2 hours. The mixture was concentrated by vacuum distillation and partially purified with reverse-phase HPLC (Phenomenex Synergi 4m Max RP 80 A column, 150×21 mm, 20 mL/min, 10-95% CH3CN/H2O 0.1% TFA, 10.5 minute gradient). After concentrating the sample by vacuum distillation, the residue was dissolved in MeOH and loaded onto an Agilent AccuBOND II SCX solid phase extraction column. After washing with MeOH, the desired compound was eluted with 2M NH3 in MeOH. The residue was partially purified using column chromatography (2M NH3 in MeOH/DCM 0-5%). The residue was purified SFC chromatography (Princeton Chromatography Pyridine column 21×250 mm, 5 um, 65 mL/min, 40° C., outlet pressure 100 bar, 220 nm, 10-50% MeOH 2% DEA/CO2, 5 minute gradient) to give a tan film (7.1 mg, 4%). HRMS (TOF) Calcd for C20H20ClN4O2+: 383.1269, found: 383.1268.

Workup

  1. concentrationThe mixture was concentrated by vacuum distillation
  2. custompartially purified with reverse-phase HPLC (Phenomenex Synergi 4m Max RP 80 A column, 150×21 mm, 20 mL/min, 10-95% CH3CN/H2O 0.1% TFA, 10.5 minute gradient)
  3. concentrationAfter concentrating the sample
  4. distillationby vacuum distillation
  5. dissolutionthe residue was dissolved in MeOH
  6. extractionloaded onto an Agilent AccuBOND II SCX solid phase extraction column
  7. washAfter washing with MeOH
  8. washthe desired compound was eluted with 2M NH3 in MeOH
  9. customThe residue was partially purified
  10. customThe residue was purified SFC chromatography (Princeton Chromatography Pyridine column 21×250 mm, 5 um, 65 mL/min, 40° C., outlet pressure 100 bar, 220 nm, 10-50% MeOH 2% DEA/CO2, 5 minute gradient)
  11. customto give a tan film (7.1 mg, 4%)

Sources & evidence

ORD record
ord-c3109a8073b04f72bdf80b0495e049d5
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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