N-Iodosuccinimide → 8-Chloro-3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazine

HRID 2402608Notes

Reaction equation

HRID 2402608 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.C1C(=O)N([I:22])C(=O)C1>CN(C)C=O.C(Cl)Cl>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:14][CH2:13][CH2:12]3)=[N:9][C:10]=2[I:22])[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 120273N-IodosuccinimideHCID 426093638-Chloro-3-cyclobutylimidazo[1,5-a]pyrazine

Product 1

HCID 426093648-Chloro-3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

8-Chloro-3-cyclobutylimidazo[1,5-a]pyrazine (1058 mg, 5.1 mmol) and NIS (1146 mg, 5.1 mmol) in anh DMF (10 mL) were stirred at 60° C. under Ar for 6 h. The reaction was diluted with DCM (˜400 mL), washed (H2O, brine), dried (Na2SO4) and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (50 g cartridge, 10:1-8:1-7:1-6:1 hexanes:EtOAc) afforded the title compound as a pale yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J=4.8 Hz, 1H), 7.26 (d, J=4.8 Hz, 1H), 3.75 (quintetd, J=1.2 Hz, 8.4 Hz, 1H), 2.62-2.42 (m, 4H), 2.32-1.98 (m, 2H); MS (ES+): m/z 334.0 (100) [MH+]; HPLC: tR=3.38 min (OpenLynx, polar—5 min).

Workup

  1. washwashed (H2O, brine)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification of the crude material by flash chromatography on silica gel (50 g cartridge, 10:1-8:1-7:1-6:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-db6d469cd37f47dc9c8ef123c63e6bdd
Source dataset
uspto-grants-2014_08
Patent number
US08796455B2

Reaction notes

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