Trifluoroacetic acid → HCID 178522238, compound

HRID 73730Notes

Reaction equation

HRID 73730 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[N:31](C4CCCCO4)[N:30]=[CH:29][CH:28]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[CH:28]=[CH:29][NH:30][N:31]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 867025946-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 178522238HCID 178522238, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Alternatively, Example 2 was prepared by treating a suspension of 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.1, 68.3 g, 132 mmol) in DCM (1 L) with TFA (305 mL, 3959 mmol) at RT for 5.5 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in EtOAc (2 L), washed with a sat. solution of NaHCO3 (3×500 mL) and brine (2×500 mL), and dried over Na2SO4. The solvent was evaporated off under reduced pressure and the residue was suspended in DCM (300 mL) and stirred at RT for 15 min. The crystalline material was filtered, washed with DCM (200 mL), dried under reduced pressure, dissolved in MeOH (500 mL) and treated with Si-Thiol (Biotage, 10.0 g, 13 mmol) for 15 h at 30° C. The mixture was filtered and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel, 2 kg, DCM/MeOH 95:5) and crystallized from MeCN to afford the title compound as a white crystalline solid.

Workup

  1. customAlternatively, Example 2 was prepared
  2. additionby treating
  3. customThe solvent was evaporated off under reduced pressure
  4. dissolutionthe residue was dissolved in EtOAc (2 L)
  5. washwashed with a sat. solution of NaHCO3 (3×500 mL) and brine (2×500 mL)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was evaporated off under reduced pressure
  8. filtrationThe crystalline material was filtered
  9. washwashed with DCM (200 mL)
  10. customdried under reduced pressure
  11. dissolutiondissolved in MeOH (500 mL)
  12. filtrationThe mixture was filtered
  13. customthe solvent was evaporated off under reduced pressure
  14. customto give the crude product which
  15. customwas purified by flash chromatography (Silica gel, 2 kg, DCM/MeOH 95:5)
  16. customcrystallized from MeCN

Sources & evidence

ORD record
ord-4920d2319e104816ba1393315162976f
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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