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

HRID 449029Notes

Reaction equation

HRID 449029 reaction equation
N#N.[Cl:3][C:4]1[C:5]([CH:10]([NH:24][C:25]([CH:27]2[CH2:31][CH2:30][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.O=P(Cl)(Cl)Cl>O.CN(C=O)C>[Cl:3][C:4]1[C:5]2[N:6]([C:25]([CH:27]3[CH2:31][CH2:30][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 4

HCID 947NitrogenHCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 86636031Cyclopentanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide

Product 1

HCID 866360308-Chloro-3-cyclopentyl-1-(4-phenoxyphenyl)-imidazo[1,5-a]pyrazineYield 0.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In an oven-dried flask filled with N2 was added cyclopentanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide (80 mg, 0.2 mol), MeCN (5 mL) and DMF (0.9 mL). POCl3 was added dropwise at 0° C. The reaction was warmed up to rt and stirred at that temp overnight. The excess of POCl3 was removed under reduced pressure and the residue was quenched with 2 N NH3 in i-PrOH 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 obtain 42 mg of the title compound as a yellow oil. Compound was carried over to the next step. MS (ES+): m/z 389.88 (30)[MH+]. HPLC: tR=4.29 min (Open Lynx, polar—5 min).

Workup

  1. customThe excess of POCl3 was removed under reduced pressure
  2. customthe residue was quenched with 2 N NH3 in i-PrOH 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-ccd97ef070324f13af7768a434cc79ab
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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