Hydrochloric Acid → HCID 42604469, compound

HRID 1689930Notes

Reaction equation

HRID 1689930 reaction equation
O=[C:2]1[NH:7][C:6]([C:8]2[CH:9]=[C:10]([O:14]C(=O)C)[CH:11]=[CH:12][CH:13]=2)=[N:5][C:4]2[CH:18]=[CH:19][S:20][C:3]1=2.P(Br)(Br)([Br:23])=O.C([O-])([O-])=O.[K+].[K+].Cl>CC#N.O>[Br:23][C:2]1[C:3]2[S:20][CH:19]=[CH:18][C:4]=2[N:5]=[C:6]([C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[N:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 24613Phosphorus oxybromideHCID 135871516HCID 135871516, compound

Product 1

HCID 42604469HCID 42604469, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of acetic acid 3-(4-oxo-3,4-dihydro-thieno[3,2-d]pyrimidin-2-yl)-phenyl ester, 27, (1.72 g, 6.0 mmol) in MeCN (25 mL) under a nitrogen atmosphere was added POBr3 (8.6 g, 30 mmol) and the resulting mixture was heated at reflux for 2.5 h. The reaction mixture was quenched by pouring onto iced water (200 mL) and the aqueous layer was neutralized by addition of solid NaHCO3. The precipitate formed was collected by filtration and dried. The resulting tan solid (1.6 g) was dissolved in THF/MeOH (1:1 v/v, 20 mL). K2CO3 (1.76 g, 12.8 mmol) was added and the mixture stirred at rt for 3.5 h. The reaction mixture was diluted with H2O (20 mL), acidified to pH 3-4 with 2M HCl and extracted with EtOAc (2×100 mL). The combined organic extracts were dried (MgSO4), concentrated and purified by flash chromatography (70:30 hexanes/EtOAc as eluent) to afford the title compound, IVa, as a colourless solid (0.76 g; 41%).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 2.5 h
  3. customThe reaction mixture was quenched
  4. additionby pouring onto iced water (200 mL)
  5. additionthe aqueous layer was neutralized by addition of solid NaHCO3
  6. customThe precipitate formed
  7. filtrationwas collected by filtration
  8. customdried
  9. dissolutionThe resulting tan solid (1.6 g) was dissolved in THF/MeOH (1:1 v/v, 20 mL)
  10. extractionextracted with EtOAc (2×100 mL)
  11. dry with materialThe combined organic extracts were dried (MgSO4)
  12. concentrationconcentrated
  13. custompurified by flash chromatography (70:30 hexanes/EtOAc as eluent)

Sources & evidence

ORD record
ord-423fed4a133740c583462f1e15378c2d
Source dataset
uspto-grants-2012_04
Patent number
US08153639B2

Reaction notes

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