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 1363489Notes

Reaction equation

HRID 1363489 reaction equation
C(=O)([O-])[O-].[Na+:5].[Na+].Br.Br[C:9]1[N:10]=[C: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 178419583HCID 178419583, compound

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-b05d5431d826481784663e4e26f8abe3
Source dataset
uspto-grants-2011_02
Patent number
US07884108B2

Reaction notes

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