Potassium Carbonate → 2-(4-((4-(6-Amino-1H-indazol-1-yl)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

HRID 515379Notes

Reaction equation

HRID 515379 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([NH2:16])[CH:14]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:16][C:13]1[CH:14]=[C:15]2[C:10]([CH:9]=[N:8][N:7]2[CH:4]2[CH2:3][CH2:2][N:1]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:25]([OH:34])([C:26]([F:27])([F:28])[F:29])[C:30]([F:31])([F:32])[F:33])=[CH:23][CH:24]=3)[CH2:6][CH2:5]2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 235273962-[4-(Bromomethyl)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-olHCID 671937121-(Piperidin-4-yl)-1H-indazol-6-amine

Product 1

HCID 866710002-(4-((4-(6-Amino-1H-indazol-1-yl)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-olYield 42.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-(Piperidin-4-yl)-1H-indazol-6-amine (3.33 mmol, 0.721 g), 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (3.33 mmol, 1.124 g) and potassium carbonate (6.67 mmol, 0.921 g) were combined and stirred overnight at room temperature in acetonitrile (15 mL). The reaction mixture was concentrated at reduced pressure and the resulting residue taken up in dichloromethane. The organic phase was washed with water and dried over sodium sulfate. The solvent was removed and the resulting residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 8% methanol/dichloromethane) to afford the title compound (664 mg). MS (ESI) m/z 473.5 [M+H]+

Workup

  1. concentrationThe reaction mixture was concentrated at reduced pressure
  2. washThe organic phase was washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed
  5. customthe resulting residue was purified by silica chromatography (
  6. washeluting with a solvent gradient from dichloromethane to 8% methanol/dichloromethane)

Sources & evidence

ORD record
ord-e5d893517d504c4fa2433c588797a809
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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