Methyl iodide → HCID 86629412, compound

HRID 420444Notes

Reaction equation

HRID 420444 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[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:24](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.CCOC(C)=O>[C:1]1([C:7]2[N:8]=[C:9]([N:17]([CH3:24])[C:18](=[O:23])[C:19]([F:22])([F:20])[F:21])[C:10]([C:13]([O:15][CH3:16])=[O:14])=[N:11][CH:12]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86629411HCID 86629411, compound

Product 1

HCID 86629412HCID 86629412, compoundYield 41.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °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. customwas carried forward to the next reaction
  2. customThe reaction flask was capped with a septum
  3. temperaturethe reaction was cooled to 23° C.
  4. washwashed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (eluant: 5-25% EtOAc/hexane)

Sources & evidence

ORD record
ord-8c54d3c8c7a647a2a3038d1785d321b6
Source dataset
uspto-grants-2012_01
Patent number
US08097620B2

Reaction notes

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