Sodium Carbonate → Methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylate

HRID 1040374

Reaction equation

HRID 1040374 reaction equation
[NH2:1][C:2]1[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:4][C:5]([Cl:9])=[C:6](Cl)[N:7]=1.[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.[Cl-].[Na+].O.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>[NH2:1][C:2]1[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH3:14])[N:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 73828Methyl 3-amino-5,6-dichloropyrazine-2-carboxylateHCID 27332672-Methylphenyl boronic acid

Product 1

HCID 86637366Methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylateYield 50%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 131718255Brine ethyl acetateSolvent

Conditions

Temperature
110 °C

Procedure

Put 5 g (22.5 mmol) of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 3.2 g (23.65 mmol) of 2-methylphenyl boronic acid in 45 mL of anhydrous toluene in a screw-top bottle. After dissolution, add 34 mL (67.6 mmol) of a 2N aqueous solution of sodium carbonate and degas the two-phase mixture for 30 min by bubbling with argon. Then add 1.3 g (1.13 mmol) of Pd(PPh3)4 and stir the reaction mixture vigorously at 110° C. for 48 h. After cooling, distribute the solution in 500 mL of EtOAc/brine 1:1 mixture and extract the aqueous phase again with 4×50 mL of EtOAc. Combine the organic phases, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 0 to 20% of EtOAc. After concentration under reduced pressure, we obtain 2 g of methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylate in the form of yellow wax.

Workup

  1. dissolutionAfter dissolution
  2. customdegas the two-phase mixture for 30 min
  3. customby bubbling with argon
  4. temperatureAfter cooling
  5. extractionextract the aqueous phase again with 4×50 mL of EtOAc
  6. dry with materialdry over Na2SO4
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue
  9. customobtained by silica gel column chromatography
  10. washeluting with a cyclohexane/EtOAc gradient from 0 to 20% of EtOAc
  11. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-1b5160dca7ae4142b9049d34884f05b1
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Linked notes

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