Trifluoroacetic acid → HCID 131732613, compound

HRID 878412Notes

Reaction equation

HRID 878412 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4](N[C@@H]2CCCC[C@@H]2NC(=O)OC(C)(C)C)[CH:3]=1.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[N:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C(F)(F)F)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:34][C:32]([F:33])([F:35])[C:28]1[N:27]=[C:26]([NH:25][C:2]2[CH:3]=[CH:4][N:5]=[CH:6][C:7]=2[C:8]#[N:9])[CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 8210242-Amino-6-(trifluoromethyl)pyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68077556HCID 68077556, compound

Product 1

HCID 131732613HCID 131732613, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl {(1S,2R)-2-[(4-chloro-5-cyanopyridin-2-yl)amino]cyclohexyl}carbamate (PrepEx 1.1) (80 mg, 0.23 mmol), 2-amino-6-(trifluoromethyl)pyridine (37 mg, 0.23 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (16 mg, 0.034 mmol), Pd2(dba)3 (21 mg, 0.023 mmol), and cesium carbonate (149 mg, 0.456 mmol) in a flask was evacuated and backfilled with nitrogen (3×). Dioxane (1.5 mL) was added, and the reaction mixture was heated to 80° C. for 3 hours. The mixture was allowed to cool to room temperature. TFA (0.386 mL, 5.02 mmol) was added, and the suspension was heated to 65° C. for 14 hours. The mixture was allowed to cool to room temperature, filtered, and concentrated under reduced pressure. The residue was dissolved in DMSO, filtered, and purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient) to afford 6-[(1R,2S)-2-aminocyclohexyl]amino}-4-{[6-(trifluoromethyl)pyridin-2-yl]amino}pyridine-3-carbonitrile. MS ESI calc'd. for C18H20F3N6 [M+H]+ 377. found 377.

Workup

  1. customwas evacuated
  2. additionDioxane (1.5 mL) was added
  3. temperatureto cool to room temperature
  4. temperaturethe suspension was heated to 65° C. for 14 hours
  5. temperatureto cool to room temperature
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in DMSO
  9. filtrationfiltered
  10. custompurified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient)

Sources & evidence

ORD record
ord-8fd08967b1874a80ace46a849cc7a030
Source dataset
uspto-grants-2015_03
Patent number
US08987456B2

Reaction notes

Loading…