2-Amino-3,5-dibromopyrazine → 5-bromo-3-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyrazin-2-amine

HRID 1628050Notes

Reaction equation

HRID 1628050 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=1)#[CH:2].Br[C:10]1[C:11]([NH2:17])=[N:12][CH:13]=[C:14]([Br:16])[N:15]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1COCC1>[Br:16][C:14]1[N:15]=[C:10]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=2)[C:11]([NH2:17])=[N:12][CH:13]=1

Participants

6

Reactant 2

HCID 6200042-Amino-3,5-dibromopyrazineHCID 511383214-Ethynyl-1-methyl-1H-pyrazole

Product 1

HCID 583821235-bromo-3-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyrazin-2-amineYield 82.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a round bottom flask was added 4-ethynyl-1-methyl-1H-pyrazole (8.5 g, 80 mmol, Preparation #Q.1), 3,5-dibromopyrazin-2-amine (16.8 g, 66.4 mmol), THF (166 mL), PdCl2(PPh3)2 (2.33 g, 3.32 mmol), copper(I) iodide (0.633 g, 3.32 mmol) and TEA (27.8 mL, 199 mmol). The mixture was heated to about 70° C. for about 1 h. The mixture was cooled to rt. The solids were filtered away and rinsed with THF (50 mL). The filtrate was partitioned with water (300 mL) and the mixture was extracted with EtOAc (400 mL). The organic layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo. The residue was triturated with EtOH (100 mL) and the solid material was collected by filtration. The mother liquor was purified by flash chromatography (300 g silica gel column, heptane/EtOAc 10:1 to 0:1) to give 5-bromo-3-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyrazin-2-amine (15.2 g, 82%): LC/MS (Table 2, Method c) Rt=1.40 min; MS m/z 278 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationThe solids were filtered away
  3. washrinsed with THF (50 mL)
  4. customThe filtrate was partitioned with water (300 mL)
  5. extractionthe mixture was extracted with EtOAc (400 mL)
  6. dry with materialThe organic layer was dried with anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with EtOH (100 mL)
  10. filtrationthe solid material was collected by filtration
  11. customThe mother liquor was purified by flash chromatography (300 g silica gel column, heptane/EtOAc 10:1 to 0:1)

Sources & evidence

ORD record
ord-f0ab0e9063324b268a0786f2c35a4e66
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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