Potassium Phosphate, Tribasic → HCID 86729378, compound

HRID 521217Notes

Reaction equation

HRID 521217 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:9][C:10]1[C:14]([C:15](=[O:17])[NH2:16])=[CH:13][N:12]([C:18]2([CH2:32][C:33]#[N:34])[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[O:25])[CH2:20][CH2:19]2)[N:11]=1.C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[C:15]([C:14]1[C:10]([NH:9][C:2]2[CH:7]=[N:6][C:5]([Cl:8])=[CH:4][CH:3]=2)=[N:11][N:12]([C:18]2([CH2:32][C:33]#[N:34])[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[O:25])[CH2:20][CH2:19]2)[CH:13]=1)(=[O:17])[NH2:16]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27344145-Bromo-2-chloropyridineHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 86729377HCID 86729377, compound

Product 1

HCID 86729378HCID 86729378, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-2-chloropyridine (206 mg, 1.07 mmol), 2,2,2-trifluoroethyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (400 mg, 1.07 mmol), Pd2(dba)3 (98 mg, 0.11 mmol), 2-di-t-butylphosphino-3,4,5,6-teramethyl-2′,4′,6′-triisopropylbiphenyl (154 mg, 0.321 mmol), and potassium phosphate (454 mg, 2.14 mmol) were combined in a 40 mL vial and dissolved in 1,4-dioxane (5.3 mL). The vial was capped, flushed with argon, and stirred at 90° C. for 2 hours. The mixture was cooled to ambient temperature and diluted with ethyl acetate. The organic layer was then washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-5% MeOH/DCM) to afford 2,2,2-trifluoroethyl 4-(4-carbamoyl-3-((6-chloropyridin-3-yl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate.

Workup

  1. customThe vial was capped
  2. customflushed with argon
  3. temperatureThe mixture was cooled to ambient temperature
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was then washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by MPLC on silica gel (
  10. washa gradient elution of 0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-82332f851cff455680116477a41047f6
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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