Sodium hydride → 5-Bromo-7-methylimidazo[1,5-a]pyrazin-8(7h)-one

HRID 518346Notes

Reaction equation

HRID 518346 reaction equation
[Br:1][C:2]1[N:3]=[CH:4][C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C1(C)C=CC(S([CH2:19][N+:20]#[C-:21])(=O)=O)=CC=1.[H-].[Na+]>C1COCC1>[Br:1][C:2]1[N:3]2[CH:19]=[N:20][CH:21]=[C:4]2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 534187885-Bromo-1-methyl-1H-pyrazin-2-one

Product 1

HCID 1180225995-Bromo-7-methylimidazo[1,5-a]pyrazin-8(7h)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromo-1-methylpyrazin-2-one (500.0 mg, 2.65 mmol) and (p-tolylsulfonyl)methyl isocyanide (573.0 mg, 2.94 mmol) in THF (4 mL) was added a suspension of NaH (235.0 mg, 5.9 mmol) in THF (2 mL) at 0° C. under N2. After stirring at 0° C. for 30 min, the mixture was stirred at 30° C. for another 1.5 h. The reaction mixture was quenched with H2O (20 mL) at 0° C., and extracted with EtOAc (30 mL×2). The organic phases were combined, washed with brine (30 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified by column chromatography (PE:EA=1/1) to give the title compound (300.0 mg, 50%) as a light yellow solid. 1H NMR (CDCl3 400 MHz) δ 8.06 (d, J=4.4 Hz, 1H), 6.61 (s, 1H), 3.48 (s, 3H). LCMS (M+H)+ 228.

Workup

  1. stirringthe mixture was stirred at 30° C. for another 1.5 h
  2. customThe reaction mixture was quenched with H2O (20 mL) at 0° C.
  3. extractionextracted with EtOAc (30 mL×2)
  4. washwashed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by column chromatography (PE:EA=1/1)

Sources & evidence

ORD record
ord-a891e163d2dd41e6a785948a9c07d268
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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