Bromine → 1-Bromo-8-chloro-3-cyclobutylimidazo[1,5-A]pyrazine

HRID 244231Notes

Reaction equation

HRID 244231 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:14][CH2:13][CH2:12]3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.[Br:15]Br>C(Cl)Cl>[Br:15][C:10]1[N:9]=[C:8]([CH:11]2[CH2:14][CH2:13][CH2:12]2)[N:4]2[CH:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=12

Participants

4

Reactant 2

HCID 24408BromineHCID 426093638-Chloro-3-cyclobutylimidazo[1,5-a]pyrazine

Product 1

HCID 576809781-Bromo-8-chloro-3-cyclobutylimidazo[1,5-A]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a clear, vigorously stirred and cooled (0° C.) solution of 8-chloro-3-cyclobutylimidazo[1,5-a]pyrazine (0.75 g, 3.6 mmol) in DCM (90 mL) was added Br2 (0.28 mL, 5.4 mmol) in DCM (90 mL) over 34 min. The reaction became a light orange suspension towards the end of the addition. Stirring was continued at the temperature for 10 min then concentrated under reduced pressure at rt. The mixture was diluted with H2O (˜20 mL), basified with 2 M aq NaOH to ˜pH 7-9 and extracted with DCM (3×80 mL). The organic layers were washed (satd aq NaHCO3, brine), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography on silica gel (50 g cartridge, 100% DCM) yielded the title compound as an off-white solid; 1H NMR (400 MHz, CD2Cl2) δ 7.41 (d, J=5.2 Hz, 1H), 7.16 (d, J=5.2 Hz, 1H), 3.70 (qud, J=1.2 Hz, 8.4 Hz, 1H), 2.48-2.33 (m, 4H), 2.13-2.02 (m, 1H), 1.98-1.88 (m, 1H); MS (ES+): m/z 286.1 (90), 288.0 (100) [MH+]; HPLC: tR=3.33 min (OpenLynx, polar—5 min).

Workup

  1. additiontowards the end of the addition
  2. stirringStirring
  3. concentrationthen concentrated under reduced pressure at rt
  4. additionThe mixture was diluted with H2O (˜20 mL)
  5. extractionextracted with DCM (3×80 mL)
  6. washThe organic layers were washed (satd aq NaHCO3, brine)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography on silica gel (50 g cartridge, 100% DCM)

Sources & evidence

ORD record
ord-84f28b59b0e14f1abec9f217197ee906
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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