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

HRID 2076456Notes

Reaction equation

HRID 2076456 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=O)C.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-64f4651cde4f4b4288f3dfe3ae7052e5
Source dataset
uspto-grants-2011_04
Patent number
US07923555B2

Reaction notes

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