Potassium Carbonate → HCID 59321826, compound

HRID 220593Notes

Reaction equation

HRID 220593 reaction equation
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Br[C:21]1[CH:26]=[CH:25][C:24]([CH:27]([CH3:30])[C:28]#[N:29])=[CH:23][CH:22]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].Cl[C:55]1[C:56]([N:61]2[CH2:66][CH2:65][N:64]([CH2:67][C:68]3[CH:69]=[N:70][N:71]([CH3:74])[C:72]=3[CH3:73])[CH2:63][CH2:62]2)=[N:57][CH:58]=[CH:59][N:60]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.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].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.O>[CH3:74][N:71]1[C:72]([CH3:73])=[C:68]([CH2:67][N:64]2[CH2:63][CH2:62][N:61]([C:56]3[C:55]([C:21]4[CH:26]=[CH:25][C:24]([CH:27]([CH3:30])[C:28]#[N:29])=[CH:23][CH:22]=4)=[N:60][CH:59]=[CH:58][N:57]=3)[CH2:66][CH2:65]2)[CH:69]=[N:70]1

Participants

11

Reactant 6

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 107509272-(4-Bromophenyl)propanenitrileHCID 594382163'-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 59321826HCID 59321826, compoundYield 107.8%

Reagents, catalysts & solvents 4

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Stir together bis(dibenzylideneacetone)palladium(0) (35 mg, 0.06 mmol) and tricyclohexylphosphine (39 mg, 0.06 mmol) in N,N-dimethylacetamide (4 mL) at room temperature under nitrogen for 20 min. Add racemic 2-(4-bromo-phenyl)-propionitrile (420 mg, 2.00 mmol), then 4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl] (521 mg, 2.05 mmol) and potassium acetate (294 mg, 3.00 mmol) and stir at 80° C. for 16 hr. Cool reaction to room temperature, add 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (307 mg, 1.00 mmol), potassium carbonate (332 mg, 2.40 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0056 mmol) and water (2 mL), then stir at 120° C. for 8 hr. Cool to room temperature, purify by SCX-2® chromatography washing with methanol then eluting with 2 M ammonia in methanol. Further purify (silica gel chromatography, eluting with 0:100 to 20:80 methanol:DCM), to give the free base racemate 2-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-propionitrile as a powder (433 mg, 107%). MS (ES): m/z=402 [M+H]+.

Workup

  1. temperatureCool
  2. customreaction to room temperature
  3. temperatureCool to room temperature
  4. custompurify by SCX-2® chromatography
  5. washwashing with methanol
  6. washthen eluting with 2 M ammonia in methanol
  7. customFurther purify
  8. wash(silica gel chromatography, eluting with 0:100 to 20:80 methanol:DCM)

Sources & evidence

ORD record
ord-c2ec44a8df104985bcfc0969fdeea687
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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