Sodium Carbonate → HCID 89544211, compound

HRID 2203400Notes

Reaction equation

HRID 2203400 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[C:5](=[O:11])[N:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([OH:31])=[C:26](B(O)O)[CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([OH:31])=[C:24]([C:2]2[N:7]3[CH:8]=[N:9][CH:10]=[C:6]3[C:5](=[O:11])[N:4]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[CH:3]=2)[CH:23]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)HCID 895440475-bromo-7-(4-methoxybenzyl)imidazo[1,5-a]pyrazin-8(7H)-one

Product 1

HCID 89544211HCID 89544211, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 5-bromo-7-(4-methoxybenzyl)imidazo[1,5-a]pyrazin-8(7H)-one (0.167 g, 0.5 mmol (prepared according to Mukaiyama, H. et al., Bioorg. Med. Chem. 2007, 15, 868-885)), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol) and (5-chloro-2-hydroxyphenyl)boronic acid in dioxane (3 mL) was added 2 M aqueous sodium carbonate (0.75 mL, 1.5 mmol). The reaction mixture was heated at 120° C. for 20 h and was allowed to cool to ambient temperature. The mixture was diluted with ethyl acetate (20 mL), filtered through a pad of sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-100% gradient of ethyl acetate in hexanes to afford 5-(5-chloro-2-hydroxyphenyl)-7-(4-methoxybenzyl)imidazo[1,5-a]pyrazin-8(7H)-one as an off-white solid in 66% yield (0.126 g): 1H NMR (300 MHz, acetone-d6) δ9.26 (br s, 1H), 7.78 (s, 1H), 7.70 (s, 1H), 7.39 (m, 4H), 7.05 (dd, J=7.7, 1.5 Hz, 1H), 6.92 (s, 1H), 6.87 (d, J=8.6 Hz, 2H), 5.05 (s, 2H), 3.74 (s, 3H); MS (ES+) m/z 382.0 (M+1), 383.9 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. filtrationfiltered through a pad of sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography
  5. washeluting with a 0-100% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-688320ffe7c54fcb8301761fc1bafa40
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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