Sodium Methoxide → HCID 66658579, compound

HRID 420445Notes

Reaction equation

HRID 420445 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([N:17](C)[C:18](=O)C(F)(F)F)[C:10]([C:13]([O:15][CH3:16])=[O:14])=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O-].[Na+]>CO.C(Cl)Cl.[Cl-].[Na+].O>[CH3:18][NH:17][C:9]1[C:10]([C:13]([O:15][CH3:16])=[O:14])=[N:11][CH:12]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=1

Participants

6

Reactant 2

HCID 10942334Sodium MethoxideHCID 86629412HCID 86629412, compound

Product 1

HCID 66658579HCID 66658579, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
23 °C

Procedure

Methyl 3-(methylamino)-5-phenylpyrazine-2-carboxylate. A solution of methyl 3-amino-5-phenylpyrazine-2-carboxylate (360 mg, 1570 μmol) in DCM (10 mL) was treated with DIPEA (547 μl, 3141 μmol) and trifluoroacetic anhydride (275 μl, 1963 μmol). The reaction stirred under nitrogen at 23° C. After 14 hours, the reaction was diluted with DCM (50 mL) and washed with water (50 mL) and brine (50 mL), dried over MgSO4, and concentrated in vacuo affording methyl 5-phenyl-3-(2,2,2-trifluoroacetamido)pyrazine-2-carboxylate as an orange solid, which was carried forward to the next reaction. A suspension of methyl 5-phenyl-3-(2,2,2-trifluoroacetamido)pyrazine-2-carboxylate (511 mg, 1571 μmol) and potassium carbonate (651 mg, 4713 μmol) in DMF (10 mL) was treated with iodomethane (196 μl, 3142 μmol). The reaction flask was capped with a septum and heated to 65° C. After 4 hours, the reaction was cooled to 23° C., diluted with EtOAc (75 mL) and washed with water (50 mL) and brine (50 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluant: 5-25% EtOAc/hexane), affording 221 mg (41%, 2 steps) of methyl 5-phenyl-3-(2,2,2-trifluoro-N-methylacetamido)pyrazine-2-carboxylate as an yellow solid. A solution of methyl 5-phenyl-3-(2,2,2-trifluoro-N-methylacetamido)pyrazine-2-carboxylate (253 mg, 746 μmol) in MeOH (2 mL) and DCM (2 mL) was treated with sodium methoxide (0.5M solution in MeOH (2983 μl, 1491 μmol)). The reaction was stirred under nitrogen at 23° C. After 90 minutes, the reaction was diluted with brine (25 mL) and extracted with DCM (3×25 mL). The combined organic layers were dried (MgSO4) and concentrated, affording 179 mg (99%) of methyl 3-(methylamino)-5-phenylpyrazine-2-carboxylate as a yellow solid. Mass: Calculated: 243.261. Observed: 244.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.37 (1H, s), 8.07-8.17 (2H, m), 7.95 (1H, br. s.), 7.46-7.55 (3H, m), 4.00 (3H, s), 3.18 (3H, d, J=4.7 Hz).

Workup

  1. extractionextracted with DCM (3×25 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-e991b11807df4c029ca545ee36e12a37
Source dataset
uspto-grants-2012_01
Patent number
US08097620B2

Reaction notes

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