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

HRID 707440Notes

Reaction equation

HRID 707440 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.O>C1COCC1>[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 3

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 86694150N2-Cyclopropylpyrazine-2,3-diamine

Product 1

HCID 866941511-CYCLOPROPYL-1H-IMIDAZO[4,5-b]PYRAZIN-2(3H)-ONEYield 71.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N2-cyclopropylpyrazine-2,3-diamine (0.6690 g, 4.45 mmol) in THF (22.27 ml) at 50° C. was added CDI (2.89 g, 17.82 mmol, Fluka). The reaction was allowed to stir for 1½ h. The reaction flask was place in an ice bath until the temperature reached 0° C. The flask was raised and water (5 mL) was added dropwise to quench. (Note: if exothermic reaction was detected then flask was placed back into ice bath until it stopped.) The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 1% to 8% MeOH in CH2Cl2, to provide 1 the title compound (0.5578 g, 3.17 mmol, 71.1% yield). LCMS showed product peak at 0.999 min (m+1=177.1). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.07 (m, 4 H) 2.87-3.00 (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. customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
  7. washeluting with a gradient of 1% to 8% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-2867559b92c047d2bbaf02b24a64ec8e
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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