Nitrogen → HCID 58102348, compound

HRID 882778Notes

Reaction equation

HRID 882778 reaction equation
Cl[C:2]1[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][N:7]=1.[C:10]1([CH3:19])[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+].N#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(COC)OC.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:10]1([CH3:19])[CH:15]=[CH:14][C:13]([C:2]2[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:12][CH:11]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 79799Tolylboronic acidHCID 2924653-Chloropyrazine-2-carbonitrile

Product 1

HCID 58102348HCID 58102348, compoundYield 126.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

3-Chloropyrazine-2-carbonitrile (3.0 g; 21.5 mmol) was dissolved in dimethoxyethane (65 ml) and 4-tolylboronic acid (3.2 g; 23.65 mmol) was added, followed by the addition of K2CO3 (8.2 g; 59 mmol) and water (30 ml). The reaction mixture was deoxygenized with N2 (g) for 3 minutes followed by the addition of triphenylphosphine (842 mg; 3.2 mmol) and palladium(II)acetate (237 mg; 1.06 mmol). The reaction mixture was heated to 90° C. for 14 h, cooled to rt, diluted with EtOAc, filtered over a plug of celite and dried with magnesiumsulfate. The organic solvent was evaporated under reduced pressure to give 5.3 g of 3-p-tolyl-pyrazine-2-carbonitrile. The intermediate nitrile was dissolved in MeOH (110 ml) followed by the addition of 4M aq NaOH (180 ml). The resulting mixture was heated to 85° C. for 14 h, cooled to rt and the MeOH was evaporated under reduced pressure. The residual aq. phase was acidified to pH=2 by the addition of conc. HCl and the precipitated product was filtered off, dissolved in DCM/EtOAc and dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 2.30 g of 3-p-tolyl-pyrazine-2-carboxylic acid. LC-MS: tR=0.40 min; [M−H]+=213.14.

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered over a plug of celite
  3. dry with materialdried with magnesiumsulfate
  4. customThe organic solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-be9dd6fbb9534f6cb135cef93057f21b
Source dataset
uspto-grants-2012_08
Patent number
US08236801B2

Reaction notes

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