Pyridine → 8-Chloro-6-methyl-imidazo[1,2-a]pyrazine

HRID 1809194Notes

Reaction equation

HRID 1809194 reaction equation
N1C=CC=CC=1.[CH3:7][C:8]1[NH:9][C:10](=O)[C:11]2[N:12]([CH:14]=[CH:15][N:16]=2)[CH:13]=1.[OH-].[Na+].O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:10]1[C:11]2[N:12]([CH:14]=[CH:15][N:16]=2)[CH:13]=[C:8]([CH3:7])[N:9]=1

Participants

5

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 457885228-Hydroxy-6-methylimidazo[1,2-a]pyrazine

Product 1

HCID 103748148-Chloro-6-methyl-imidazo[1,2-a]pyrazineYield 35%

Conditions

Temperature
120 °C

Procedure

Pyridine (0.4 mL, 4.9 mmol) was added to a solution of 6-methyl-7H-imidazo[1,2-a]pyrazin-8-one (0.97 g, 6.5 mmol) in POCl3 (19 mL) and the reaction is stirred at 120° C. under N2 atmosphere for 4 h 30 min. The reaction is cooled to 60° C. and poured into 60 g of ice and stirred for 1 h. The solution is neutralized with NaOH (10%), extracted with CHCl3/IPA 9/1, dried with MgSO4 anh., filtered and concentrated. The crude product is purified by column chromatography using a gradient of (DCM/MeOH:99/1 to 95/5) to give 8-chloro-6-methyl-imidazo[1,2-a]pyrazine as a pale yellow solid (0.383 g, 35%).

Workup

  1. temperatureThe reaction is cooled to 60° C.
  2. stirringstirred for 1 h
  3. extractionextracted with CHCl3/IPA 9/1
  4. dry with materialdried with MgSO4 anh.
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by column chromatography

Sources & evidence

ORD record
ord-f08c52e6859e49248d2d83f57aac179f
Source dataset
uspto-grants-2013_01
Patent number
US08362018B2

Reaction notes

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