Sodium Carbonate → Methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate

HRID 1639930Notes

Reaction equation

HRID 1639930 reaction equation
C1(P(CCCC)C2C=CC=CC=2)C=CC=CC=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:26]([O:28][CH3:29])=[O:27])=[N:23][C:24]=1Br.[CH2:30]([O:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][C:43]=1[Cl:44])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.CCOC(C)=O.[Pd].C(#N)C1C=CC=CC=1.C(#N)C1C=CC=CC=1.C(O)C>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:26]([O:28][CH3:29])=[O:27])=[N:23][C:24]=1[C:40]1[CH:41]=[CH:42][C:43]([Cl:44])=[C:38]([O:37][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:39]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 80755ButyldiphenylphosphineHCID 23005378(3-(Benzyloxy)-4-chlorophenyl)boronic acidHCID 29983315Methyl 5-amino-6-bromopyrazine-2-carboxylate

Product 1

HCID 66721267Methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylateYield 50.3%

Reagents, catalysts & solvents 4

HCID 86637365(Bis-benzonitrile)-palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 22728543Water ethylacetateSolvent

Procedure

Stir a suspension of 137 mg (0.36 mmol) of (bis-benzonitrile)-palladium II dichloride and 183 mg (0.43 mmol) of diphenylphosphinobutane in 7 mL of toluene under argon for 30 min at room temperature. Then add, while bubbling with argon, 1.66 g (7.15 mmol) of methyl 5-amino-6-bromopyrazine-2-carboxylate, 1.97 g (7.51 mmol) of [3-(benzyloxy)-4-chlorophenyl]boronic acid, 2.4 mL of ethanol and 3.58 mL (7.15 mmol) of a 2N aqueous solution of sodium carbonate. Reflux the reaction mixture for 5 h 30 min and then distribute in 100 mL of a water/EtOAc 1:1 mixture. Wash the organic phase with 50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue, obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 50 to 100% of EtOAc. After concentration under reduced pressure, we obtain 1.33 g of methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate in the form of yellow wax.

Workup

  1. additionThen add
  2. temperatureReflux the reaction mixture for 5 h 30 min
  3. washWash the organic phase with 50 mL of water
  4. dry with materialdry over Na2SO4
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue
  7. customobtained by silica gel column chromatography
  8. washeluting with a cyclohexane/EtOAc gradient from 50 to 100% of EtOAc
  9. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-3a76b22b544d4c0d902cc53e10b1a9eb
Source dataset
uspto-grants-2012_02
Patent number
US08110579B2

Reaction notes

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