1,1'-Carbonyldiimidazole → 1-CYCLOPROPYL-1H-IMIDAZO[4,5-b]PYRAZIN-2(3H)-ONE

HRID 707282Notes

Reaction equation

HRID 707282 reaction equation
[CH:1]1([NH:4][C:5]2[C:10]([NH2:11])=[N:9][CH:8]=[CH:7][N:6]=2)[CH2:3][CH2:2]1.C1N=CN([C:17](N2C=NC=C2)=[O:18])C=1>C1COCC1.O>[CH:1]1([N:4]2[C:5]3=[N:6][CH:7]=[CH:8][N:9]=[C:10]3[NH:11][C:17]2=[O:18])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86694150N2-Cyclopropylpyrazine-2,3-diamine

Product 1

HCID 866941511-CYCLOPROPYL-1H-IMIDAZO[4,5-b]PYRAZIN-2(3H)-ONEYield 41.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N2-cyclopropylpyrazine-2,3-diamine (2.0003 g, 13.32 mmol) in THF (66.6 ml) at 50° C. was added CDI (8.64 g, 53.3 mmol, Fluka) and stirred. The reaction flask was place in an ice bath until temperature reached 0° C. The flask was raised and water (10 mL) was added dropwise to quench. (Note: if exothermic reaction was detected then flask was placed back into ice bath until it stopped.) The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, saturated NaCl, dried over MgSO4, filtered and concentrated in vacuo. NMR showed product and imidazole. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (100 g), eluting with a gradient of 1% to 6% MeOH in CH2Cl2, to provide the title compound (0.9715 g, 5.51 mmol, 41.4% yield). LCMS showed product peak at 1.00 min (m+1=177.1) 1H NMR (400 MHz, DMSO-d) δ ppm 0.94-1.02 (m, 2 H) 1.02-1.08 (m, 2 H) 2.89-3.00 (m, 1 H) 7.84-7.89 (m, 1 H) 7.89-7.94 (m, 1 H) 11.87 (s, 1 H).

Workup

  1. customreached 0° C
  2. temperatureThe flask was raised
  3. customto quench
  4. custom(Note: if exothermic reaction
  5. customflask was placed back into ice bath until it
  6. extractionextracted with EtOAc
  7. extractionThe organic extract
  8. washwas washed with water, saturated NaCl
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customchromatographed through a Biotage SNAP HP-silica gel column (100 g)
  13. washeluting with a gradient of 1% to 6% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-71f5d693b297495d951863599e56920a
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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