Sodium Carbonate → 3-Phenylimidazo[1,2-a]pyrazine

HRID 1893402Notes

Reaction equation

HRID 1893402 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.C(=O)([O-])[O-].[Na+].[Na+].[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[C:17]1([C:2]2[N:6]3[CH:7]=[CH:8][N:9]=[CH:10][C:5]3=[N:4][CH:3]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 27716713-Bromoimidazo(1,2-a)pyrazine2×

Product 1

HCID 208103403-Phenylimidazo[1,2-a]pyrazineYield 88%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-Bromoimidazo[1,2-a]pyrazine (1.66 g, 7.13 mmol, Intermediate 2), sodium carbonate (3.78 g, 35.6 mmol) and phenylboronic acid (1.043 g, 8.55 mmol) were dissolved in 1,2-dimethoxyethane (DME) (40 ml) and water (20 ml). Bis(triphenylphosphine)palladium (II) chloride (0.250 g, 0.356 mmol) was added and the biphasic solution heated at 80° C. for 16 h. The aqueous phase was extracted with ethyl acetate (3×100 ml) and the combined extracts washed with saturated sodium bicarbonate solution (100 ml), water (100 ml), brine (100 ml) and dried by passing through a hydromatrix cartridge (Varian). The filtrate was concentrated in vacuo to afford a crude oil (2.44 g). The crude product was purified by flash chromatography (Biotage SP4, 40+M, eluting with a 0-100% gradient of ethylacetate in hexane)—(the product elutes in 100% ethyl acetate), to afford 3-phenylimidazo[1,2-a]pyrazine (1.22 g, 6.25 mmol, 88% yield).

Workup

  1. extractionThe aqueous phase was extracted with ethyl acetate (3×100 ml)
  2. washthe combined extracts washed with saturated sodium bicarbonate solution (100 ml), water (100 ml), brine (100 ml)
  3. customdried
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto afford a crude oil (2.44 g)
  6. customThe crude product was purified by flash chromatography (Biotage SP4, 40+M
  7. washeluting with a 0-100% gradient of ethylacetate in hexane)—(the product

Sources & evidence

ORD record
ord-7bbf034828d5441aa441ce65425fc294
Source dataset
uspto-grants-2013_08
Patent number
US08513248B2

Reaction notes

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