Bromoacetone → 6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazine

HRID 402881Notes

Reaction equation

HRID 402881 reaction equation
Br[CH2:2][C:3](=O)[CH3:4].[C:6]([SiH2:10][O:11][C:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:13]1[N:14]=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=1)([CH3:9])([CH3:8])[CH3:7].C([O-])(O)=O.[Na+]>COCCOC.S1(CCCC1)(=O)=O>[C:6]([SiH2:10][O:11][C:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:13]1[N:14]=[CH:15][C:16]2[N:17]([CH:2]=[C:3]([CH3:4])[N:19]=2)[CH:18]=1)([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 3

HCID 11715BromoacetoneHCID 516892Sodium BicarbonateHCID 178455413HCID 178455413, compound

Product 1

HCID 1317297536-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyrazineYield 40%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
50 °C

Procedure

Bromoacetone (4.3 g, 31.4 mmol, 2.9 equiv) is added to a solution of 5-(tert-butyl-diphenyl-silanyloxymethyl)-pyrazin-2-ylamine (4.0 g, 10.7 mmol) in 1,2-dimethoxyethane (20 ml) and sulfolane (20 ml). The reaction mixture is stirred overnight at 50° C. Then a 10% aqueous solution of NaHCO3 (30 ml) is added, and the mixture is heated to reflux for 1 hour. After cooling, the mixture is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (hexane/EtOAc 3:1) affords the title compound (1.7 g, 40%). 1H NMR (400 MHz, d6-DMSO): δ=8.78 (d, J=0.9 Hz, 1H), 8.43 (d, J=1.4 Hz, 1H), 7.92 (s, 1H), 7.63-7.61 (m, 4H); 7.41-7.35 (m, 6H), 4.72 (s, 2H), 2.34 (s, 3H), 1.00 (s, 9H). MS (ES+): 402 (M+H)+.

Workup

  1. temperaturethe mixture is heated
  2. temperatureto reflux for 1 hour
  3. temperatureAfter cooling
  4. extractionthe mixture is extracted three times with EtOAc
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (hexane/EtOAc 3:1)

Sources & evidence

ORD record
ord-c4997d862e7e4373998e1f94cccdec66
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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