Sodium Carbonate → Sodium 4-methyl-6-(2-methyl-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-olate

HRID 888429

Reaction equation

HRID 888429 reaction equation
C(=O)([O-])[O-].[Na+:5].[Na+].Br.Br[C:9]1[NH:10][CH:11]([OH:17])[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=1.[CH3:18][C:19]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=[CH:21][C:20]=1[NH:34][C:35]([C:37]1[S:41][C:40]2[CH2:42][CH2:43][CH2:44][CH2:45][C:39]=2[CH:38]=1)=[O:36]>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.O1CCOCC1>[CH3:15][N:13]1[CH:14]=[C:9]([C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([NH:34][C:35]([C:37]3[S:41][C:40]4[CH2:42][CH2:43][CH2:44][CH2:45][C:39]=4[CH:38]=3)=[O:36])[C:19]=2[CH3:18])[N:10]=[C:11]([O-:17])[C:12]1=[O:16].[Na+:5]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58729134N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideHCID 698102975-Bromo-3-hydroxy-1-methyl-4H-pyrazin-2-one hydrogen bromide salt

Product 1

HCID 57625105Sodium 4-methyl-6-(2-methyl-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-olateYield 53.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 250-mL three-neck round-bottomed flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (100 mL) and aqueous 2.0 M sodium carbonate (15 mL, 29.5 mmol). After bubbling nitrogen through the resulting solution for 15 minutes, 5 (8.44 g, 29.5 mmol), 9 (12.9 g, 32.5 mmol) and tetrakis(triphenylphosphine)palladium (2.38 g, 2.06 mmol) were added and the reaction mixture then heated at reflux for 20 h. After this time the reaction was cooled to room temperature and filtered through a pad of Celite 521. The filter cake was washed with a 1:1 solution of methanol/methylene chloride (350 mL) and the filter cake discarded. On standing a precipitate formed in the filtrate and this solid was filtered. The filter cake was triturated with ethyl acetate (50 mL), filtered and dried under vacuum. The resulting solid was suspended in water (75 mL), filtered and the filter cake washed with water (25 mL). The filter cake was dried to a constant weight to give a 53% yield (6.57 g) of 10 as a light yellow solid: mp 225-230° C. dec, 1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.66 (s, 1H), 7.21 (m, 1H), 7.16 (m, 2H), 6.37 (s, 1H), 2.75 (m, 2H), 2.61 (m, 2H), 2.20 (s, 3H), 1.77 (m, 4H); MS (ESI+) m/z 418 (M+H).

Workup

  1. customA 250-mL three-neck round-bottomed flask equipped with a mechanical stirrer
  2. temperaturereflux condenser and nitrogen inlet
  3. customAfter bubbling nitrogen through the resulting solution for 15 minutes
  4. temperaturethe reaction mixture then heated
  5. temperatureat reflux for 20 h
  6. filtrationfiltered through a pad of Celite 521
  7. washThe filter cake was washed with a 1:1 solution of methanol/methylene chloride (350 mL)
  8. customformed in the filtrate
  9. filtrationthis solid was filtered
  10. customThe filter cake was triturated with ethyl acetate (50 mL)
  11. filtrationfiltered
  12. customdried under vacuum
  13. filtrationfiltered
  14. washthe filter cake washed with water (25 mL)
  15. customThe filter cake was dried to a constant weight

Sources & evidence

ORD record
ord-a103bc160d29487598dbe94bf1ede063
Source dataset
uspto-grants-2012_08
Patent number
US08247550B2

Linked notes

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