Pyridine → 8-Chloro-3-(3-methyloxetan-3-yl)imidazo[1,5-a]pyrazine

HRID 245682Notes

Reaction equation

HRID 245682 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([C:12]2([CH3:16])[CH2:15][O:14][CH2:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>ClCCl>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([C:12]3([CH3:16])[CH2:15][O:14][CH2:13]3)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 86674645N-((3-chloropyrazin-2-yl)methyl)-3-methyloxetane-3-carboxamide

Product 1

HCID 866746468-Chloro-3-(3-methyloxetan-3-yl)imidazo[1,5-a]pyrazineYield 128.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-((3-chloropyrazin-2-yl)methyl)-3-methyloxetane-3-carboxamide (1.945 mmol, 0.47 g) in dichloromethane (10 ml) cooled in an ice-bath was added pyridine (27.2 mmol, 2.198 ml) and trifluoromethane sulfonic anhydride (11.67 mmol, 1.971 ml). The ice-bath was removed and the reaction was stirred at room temperature. After 2 hours the reaction mixture was cooled in ice-bath, diluted with ethyl acetate (5 mL) and quenched with aqueous sodium hydrogencarbonate. The organic layer separated and the aqueous layer washed four times with ethyl acetate. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. Purification by column chromatography (silica gel, ethyl acetate) yielded 8-chloro-3-(3-methyloxetan-3-yl)imidazo[1,5-a]pyrazine (0.56 g).

Workup

  1. customThe ice-bath was removed
  2. temperatureAfter 2 hours the reaction mixture was cooled in ice-bath
  3. additiondiluted with ethyl acetate (5 mL)
  4. customquenched with aqueous sodium hydrogencarbonate
  5. customThe organic layer separated
  6. washthe aqueous layer washed four times with ethyl acetate
  7. dry with materialThe combined organic extracts were dried (sodium sulfate)
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-0e6db191ac6f4b3aadc207f52e251549
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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