Potassium Phosphate, Tribasic → HCID 45275458, compound

HRID 1622365Notes

Reaction equation

HRID 1622365 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:17])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:17][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:30])([F:29])[F:18])=[CH:21][CH:22]=2)[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 45275245HCID 45275245, compound

Product 1

HCID 45275458HCID 45275458, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
170 °C

Procedure

To a solution of 1-(3,5-dibromopyridin-4-yl)piperidine-4-carboxamide E27 (50 mg, 0.14 mmol), 4-trifluoromethylbenzene boronic acid (0.11 g, 0.56 mmol) and potassium phosphate (0.20 g, 0.96 mmol) in toluene (4 mL) was added tetrakis(triphenylphosphine)palladium(0) (18 mg, 10 mol %). The mixture was heated at 170° C. in a microwave reactor for 60 min, then poured into a saturated solution of sodium hydrogencarbonate (25 mL). The mixture was extracted with EtOAc (2×20 mL) and the combined organic extracts were washed with water (25 mL), brine (25 mL), dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography on silica gel (CH2Cl2, MeOH, 98:2) and further purified preparative hplc (H2O, MeCN, gradient 90:10 to 10:90 over 30 min) (11 mg, 9%), m/z (ESI) C18H18BrF3N3O requires 428.0580 found [M+H]+ 428.0574.

Workup

  1. extractionThe mixture was extracted with EtOAc (2×20 mL)
  2. washthe combined organic extracts were washed with water (25 mL), brine (25 mL)
  3. dry with materialdried (MgSO4)
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by flash column chromatography on silica gel (CH2Cl2, MeOH, 98:2) and further purified preparative hplc (H2O, MeCN, gradient 90:10 to 10:90 over 30 min) (11 mg, 9%), m/z (ESI) C18H18BrF3N3O

Sources & evidence

ORD record
ord-5426ea01216e41a2a6f30847224c2dd2
Source dataset
uspto-grants-2014_07
Patent number
US08778925B2

Reaction notes

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