3-{1-[3-(Benzyloxy)phenyl]-8-chloroimidazo[1,5-a]pyrazin-3-yl}cyclobutanone → 3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol

HRID 2373884Notes

Reaction equation

HRID 2373884 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][C:27](=[O:29])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:30][Mg+].[Br-]>C1COCC1.C1(C)C=CC=CC=1.C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][C:27]([CH3:30])([OH:29])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 598528193-{1-[3-(Benzyloxy)phenyl]-8-chloroimidazo[1,5-a]pyrazin-3-yl}cyclobutanoneHCID 178418689HCID 178418689, compound

Product 1

HCID 598527383-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-78 °C

Procedure

3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanone (100 mg, 248 mols) was dissolved in dry THF (1.0 mL) under inert atmosphere and cooled to −78° C. A solution of MeMgBr (40 μL, 322 mols) in toluene: THF (75:25) was added slowly to the cooled solution. After 24 h of reaction at rt the reaction was cooled to 0° C. and quenched with NH4Cl sat. aq. solution and the aqueous layer was washed with EtOAc (2×). The organic layers where combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude oil was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 2-5% ((7N NH3) in MeOH):CH2Cl2], yielding 3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol as a brown solid.

Workup

  1. customAfter 24 h of reaction at rt the reaction
  2. temperaturewas cooled to 0° C.
  3. customquenched with NH4Cl sat. aq. solution
  4. washthe aqueous layer was washed with EtOAc (2×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude oil was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 2-5% ((7N NH3) in MeOH):CH2Cl2]

Sources & evidence

ORD record
ord-7a84ee07003b48fc806dca3f1aba385e
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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