2-Amino-3,5-dibromopyrazine → HCID 86691096, compound

HRID 1406277Notes

Reaction equation

HRID 1406277 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1.[NH2:13][C:14]1[C:19](Br)=[N:18][C:17]([Br:21])=[CH:16][N:15]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>O1CCCC1>[Br:21][C:17]1[N:18]=[C:19]([O:10][CH:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:11][CH3:12])[CH3:9])[C:14]([NH2:13])=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 6200042-Amino-3,5-dibromopyrazineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 448910741-(5-Fluoro-2-methoxyphenyl)ethan-1-ol

Product 1

HCID 86691096HCID 86691096, compoundYield 52.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
66 °C

Procedure

To a solution of 1-(5-fluoro-2-methoxy-phenyl)-ethanol (33.6 g, 197 mmol, 1.5 eq.) in tetrahydrofuran (140 mL) was added 2-amino-3,5-dibromo-pyrazine (39.9 g, 158 mmol) followed by a solution of sodium hexamethyldisilazide (1M in tetrahydrofuran, 200 mL, 1.5 eq.). This mixture was then heated to 66° C. for 4 hr before cooling and evaporating under reduced pressure. The residue was purified by chromatography on silica gel (100 g) eluting with tert-butyl methyl ether to give an orange solid after evaporating under reduced pressure. This solid was slurried in ice cold methanol and filtered to give the title compound as a beige solid (28.4 g, 42%).

Workup

  1. temperaturebefore cooling
  2. customevaporating under reduced pressure
  3. customThe residue was purified by chromatography on silica gel (100 g)
  4. washeluting with tert-butyl methyl ether
  5. customto give an orange solid
  6. customafter evaporating under reduced pressure
  7. filtrationfiltered

Sources & evidence

ORD record
ord-4fbc903c3c9046bdb996a713890fbe66
Source dataset
uspto-grants-2014_12
Patent number
US08916593B2

Reaction notes

Loading…