Nitrogen → 8-Chloro-3-cyclopropyl-1-(4-phenoxyphenyl)-imidazo[1,5-a]pyrazine

HRID 449026Notes

Reaction equation

HRID 449026 reaction equation
N#N.[Cl:3][C:4]1[C:5]([CH:10]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=O)[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[N:6][CH:7]=[CH:8][N:9]=1.CC#N.CN(C=O)C.O=P(Cl)(Cl)Cl>O>[Cl:3][C:4]1[C:5]2[N:6]([C:25]([CH:27]3[CH2:29][CH2:28]3)=[N:24][C:10]=2[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[CH:7]=[CH:8][N:9]=1

Participants

7

Reactant 5

HCID 947NitrogenHCID 6228DimethylformamideHCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 86636029Cyclopropanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide

Product 1

HCID 866360288-Chloro-3-cyclopropyl-1-(4-phenoxyphenyl)-imidazo[1,5-a]pyrazine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In an oven-dried flask filled with N2 was added cyclopropanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide (55 mg, 0.00014 mol), MeCN (4 mL, 0.07 mol) and DMF (0.7 mL, 0.009 mol). POCl3 was added dropwise at 0° C. The reaction mixture was warmed up to rt and stirred at that temperature overnight. The excess of POCl3 was removed under reduced pressure and the residue was quenched with solution of NH3 in i-PrOH (2 N) at 0° C. with vigorous stirring to adjust pH to 9. The crude reaction mixture was then charged with water and the aqueous layer was washed with DCM. The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound, which was used in next step without further purification.

Workup

  1. customThe excess of POCl3 was removed under reduced pressure
  2. customthe residue was quenched with solution of NH3 in i-PrOH (2 N) at 0° C.
  3. stirringwith vigorous stirring
  4. customThe crude reaction mixture
  5. washthe aqueous layer was washed with DCM
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-12dfae03fb294ba9b6848bcf26992516
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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