Potassium Phosphate, Tribasic → (2-(4-Chloro-phenyl)-2-[4-(1H-pyrazol-4-yl)-phenyl]-ethyl)-methyl-amine

HRID 924727Notes

Reaction equation

HRID 924727 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][NH:30][CH:31]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.CO.C1(C)C=CC=CC=1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:27]3[CH:28]=[N:29][NH:30][CH:31]=3)=[CH:3][CH:4]=2)[CH2:9][NH:10][CH3:11])=[CH:13][CH:14]=1

Participants

9

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57691393[2-(4-Bromo-phenyl)-2-(4-chloro-phenyl)ethyl]-methyl-amine

Product 1

HCID 11438353(2-(4-Chloro-phenyl)-2-[4-(1H-pyrazol-4-yl)-phenyl]-ethyl)-methyl-amineYield 84.2%

Reagents, catalysts & solvents 5

HCID 178418851HCID 178418851, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of [2-(4-Bromo-phenyl)-2-(4-chloro-phenyl)-ethyl]-methyl-amine (6.1 g, 13.716 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.3 g, 27.431 mmol) and K3PO4 (10.19 g, 48.00 mmol) in ethanol (7.5 ml), methanol (11.5 ml), toluene (7.5 ml) and water (11.5 ml) was purged with nitrogen for 2 minutes. Bis(tri-t-butylphosphine)palladium (0) (175 mg, 2.5 mol %) was then added and the reaction mixture purged with nitrogen for a further 2 minutes. The mixture was then heated to 80° C., under nitrogen for a period of 17 hours. The solvents were removed and the residue was partitioned between ethyl acetate and 2N NaOH. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography (SiO2), eluting with dichloromethane:methanol:acetic acid:water (90:18:3:2) to afford the title compound (3.6 g); LCMS (PS-A2) Rt 2.08 min [M+H]+ 312.

Workup

  1. customthe reaction mixture purged with nitrogen for a further 2 minutes
  2. customThe solvents were removed
  3. customthe residue was partitioned between ethyl acetate and 2N NaOH
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude reaction mixture
  9. customwas purified by column chromatography (SiO2)
  10. washeluting with dichloromethane:methanol:acetic acid:water (90:18:3:2)

Sources & evidence

ORD record
ord-bf1b292e58054f749522f5550a827cd8
Source dataset
uspto-grants-2016_03
Patent number
US09283226B2

Reaction notes

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