Potassium Phosphate, Tribasic → [1,1'-Biphenyl]-2-carbonitrile, 3'-imidazo[1,2-a]pyrazin-3-yl-

HRID 895118Notes

Reaction equation

HRID 895118 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][N:9]=[CH:10][C:5]2=[N:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]([C:33]3[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:30]=[CH:31][CH:32]=2)O1>CN(C)C(=O)C.O.C(=O)([O-])O.[Na+].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>[N:4]1[CH:3]=[C:2]([C:31]2[CH:30]=[C:29]([C:33]3[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:28]=[CH:27][CH:32]=2)[N:6]2[CH:7]=[CH:8][N:9]=[CH:10][C:5]=12

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27716713-Bromoimidazo(1,2-a)pyrazineHCID 112436553'-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile

Product 1

HCID 9817662[1,1'-Biphenyl]-2-carbonitrile, 3'-imidazo[1,2-a]pyrazin-3-yl-Yield 37%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromoimidazo[1,2-α]pyrazine (150 mg, 0.76 mmol), potassium phosphate (321 mg, 1.51 mmol) and 3′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile (3 ml of a 0.5M solution in N,N-dimethylacetamide) were degassed with N2 for 15 min. Tetrakis(triphenylphosphine)palladium(0) (44 mg, 0.04 mmol) was added and the mixture heated at 80° C. for 18 h. The reaction was allowed to cool to room temperature, diluted with water (20 ml) and saturated sodium hydrogencarbonate solution (20 ml) then extracted with ethyl acetate (2×75 ml). The combined organic fractions were washed with brine (40 ml), dried over anhydrous sodium sulfate and evaporated to give a black oil. The oil was purified by silica gel chromatography eluting with dichloromethane and 1% 0.88 ammonia on a gradient of methanol (1-2%). The solid obtained was triturated with diethyl ether which gave 3′-(imidazo[1,2-α]pyrazin-3-yl)biphenyl-2-carbonitrile (83 mg, 37%) as a white powder: δH (400 MHz, CDCl3) 7.52 (1H, td, J 8 and 1), 7.58 (1H, dd, J 8 and 1), 7.61-7.74 (4H, m), 7.80-7.85 (2H, m), 7.94-7.97 (2H, m), 8.55 (1H, d), 9.18 (1H, s).

Workup

  1. customwere degassed with N2 for 15 min
  2. temperatureto cool to room temperature
  3. extractionthen extracted with ethyl acetate (2×75 ml)
  4. washThe combined organic fractions were washed with brine (40 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customto give a black oil
  8. customThe oil was purified by silica gel chromatography
  9. washeluting with dichloromethane and 1% 0.88 ammonia on a gradient of methanol (1-2%)
  10. customThe solid obtained
  11. customwas triturated with diethyl ether which

Sources & evidence

ORD record
ord-821a43c3a85d4a6391410636e2be429b
Source dataset
uspto-grants-2005_07
Patent number
US06914063B2

Reaction notes

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