3-Hydroxypyridine → HCID 54596306, compound

HRID 1853147Notes

Reaction equation

HRID 1853147 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:17])=[N:12][CH:13]=[C:14](Br)[N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=1>CN(C=O)C.[Cu]>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:17])=[N:12][CH:13]=[C:14]([O:30][C:26]2[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=2)[N:15]=1

Participants

6

Reactant 3

HCID 79713-HydroxypyridineHCID 10796Cesium carbonateHCID 529377603-(1H-benzo[d]imidazol-2-yl)-5-bromopyrazin-2-amine

Product 1

HCID 54596306HCID 54596306, compoundYield 11.4%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Procedure

3-(1H-Benzimidazol-2-yl)-5-bromo-pyrazin-2-amine (100 mg, 0.3447 mmol), dicesium carbonate (366 mg, 1.034 mmol), copper (2.2 mg, 0.034447 mmol) and pyridin-3-ol (327.8 mg, 3.447 mmol) in DMF (2 mL) were heated at 130° C. under microwave conditions for 1 hour. The reaction mixture was filtered through a pad of silica eluting with 90 to 100% EtOAc/Petroleum Ether and the relevant fractions concentrated in vacuo. The resiude was redissolved in EtOAc and washed with saturated aqueous NaHCO3 (×2) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (12 mg, 11% Yield). 1H NMR (400.0 MHz, CDCl3) δ 7.33-7.38 (2H, m), 7.77-7.8 (2H, m), 7.82-7.88 (1H, m), 8.05-8.1 (1H, m), 8.15 (1H, s), 8.8-8.55 (1H, m) and 10.2 (1H, s) ppm; MS (ES+) 305.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of silica eluting with 90 to 100% EtOAc/Petroleum Ether
  2. concentrationthe relevant fractions concentrated in vacuo
  3. dissolutionThe resiude was redissolved in EtOAc
  4. washwashed with saturated aqueous NaHCO3 (×2) and brine (×1)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-9e359ddee1ec42fa8dfa0abe84e1ae7b
Source dataset
uspto-grants-2015_02
Patent number
US08962631B2

Reaction notes

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