Sodium Carbonate → HCID 178498934, compound

HRID 1746195Notes

Reaction equation

HRID 1746195 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[S:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10](Br)[CH:9]=2)=[O:4].[N:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[N:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.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>[CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[S:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([C:22]1[CH:23]=[N:18][CH:19]=[N:20][CH:21]=1)[CH:9]=2)=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 178498916HCID 178498916, compound

Product 1

HCID 178498934HCID 178498934, compoundYield 35.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 7-bromo-4-hydroxy-2-oxo-2H-thiochromene-3-carboxylic acid methyl ester (Example 5 e) (220 mg, 0.70 mmol) in dimethoxyethane (DME) (3.1 mL) was added pyrimidine-5-yl boronic acid (104 mg, 0.84 mmol), Pd(PPh3)4 solid (65 mg, 0.08 mmol) and then 2M aqueous Na2CO3 solution (0.86 mL). The resulting mixture was purged with nitrogen gas for 1 min and heated to reflux for 2 h. After cooling, the reaction mixture was diluted with water (80 mL), acidified using 1 N HCl to pH 3-4 and extracted with EtOAc. The two phases were filtered through a pad of Celite® to form two clear layers. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated with MeOH (10 mL) and the solid collected, rinsed with MeOH (2 mL) and dried in vacuo to provide 4-hydroxy-2-oxo-7-pyrimidin-5-yl-2H-thiochromene-3-carboxylic acid methyl ester (79 mg). MS ESI(−) m/e: 313.09 (M−1).

Workup

  1. customThe resulting mixture was purged with nitrogen gas for 1 min
  2. temperatureheated
  3. temperatureto reflux for 2 h
  4. temperatureAfter cooling
  5. additionthe reaction mixture was diluted with water (80 mL)
  6. extractionextracted with EtOAc
  7. filtrationThe two phases were filtered through a pad of Celite®
  8. customto form two clear layers
  9. customThe organic layer was separated
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was triturated with MeOH (10 mL)
  15. customthe solid collected
  16. washrinsed with MeOH (2 mL)
  17. customdried in vacuo

Sources & evidence

ORD record
ord-60f5c8b4961e4d9f8ac7668cedf77dc0
Source dataset
uspto-grants-2015_10
Patent number
US09149476B2

Reaction notes

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