HCID 13365017, compound → HCID 13365018, compound

HRID 1154565Notes

Reaction equation

HRID 1154565 reaction equation
[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[N:6][C:7](=[O:15])[NH:8]2.[CH3:16][Mg]Br>O1CCCC1.CCOCC>[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]([CH3:16])[NH:6][C:7](=[O:15])[NH:8]2

Participants

5

Reactant 2

HCID 13365017HCID 13365017, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 13365018HCID 13365018, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a partial solution of 5,6-dimethoxy-2(1H)quinazolinone (10.0 g, 48.5 mM) in dry tetrahydrofuran (1100 ml) under nitrogen, is added at 0° C. over 20 minutes, an excess of methyl magnesium bromide in ether (62.60 ml of a 3.1M solution in ether, 194.06 mM). The reaction mixture is then removed from the cooling bath, allowed to reach room temperature and is stirred at room temperature for 16 hours. Additional methyl magnesium bromide is added (15.65 ml of a 3.1M solution in ether; 48.52 mM) and the reaction mixture is heated at reflux for 2 hours, cooled in an ice-water bath and an aqueous solution of NH4Cl (100 ml of saturated NH4Cl and 100 ml H2O) is added with stirring. After the addition is complete, 10% aqueous HCl is added until a pH of ~6.0 is reached. The layers are separated and the aqueous layer is extracted with CHCl3 (3× 250 ml). The CHCl3 extract is combined with the previously separated tetrahydrofuran layer, and the combined organic layers are washed with a saturated aqueous solution of NaCl (200 ml) and dried (Na2SO4). Filtration followed by concentration to ~250 ml affords an off-white precipitate which is filtered and recrystallized from isopropanol (200 ml) to give the product as a colorless solid; yield 9.7 g (87.8%), m.p. 210°-212° C.

Workup

  1. customThe reaction mixture is then removed from the cooling bath
  2. customto reach room temperature
  3. additionAdditional methyl magnesium bromide is added (15.65 ml of a 3.1M solution in ether
  4. temperature48.52 mM) and the reaction mixture is heated
  5. temperatureat reflux for 2 hours
  6. temperaturecooled in an ice-water bath
  7. additionan aqueous solution of NH4Cl (100 ml of saturated NH4Cl and 100 ml H2O) is added
  8. stirringwith stirring
  9. additionAfter the addition
  10. addition10% aqueous HCl is added until a pH of ~6.0
  11. customThe layers are separated
  12. extractionthe aqueous layer is extracted with CHCl3 (3× 250 ml)
  13. extractionThe CHCl3 extract
  14. washthe combined organic layers are washed with a saturated aqueous solution of NaCl (200 ml)
  15. dry with materialdried (Na2SO4)
  16. filtrationFiltration
  17. concentrationfollowed by concentration to ~250 ml
  18. customaffords an off-white precipitate which
  19. filtrationis filtered
  20. customrecrystallized from isopropanol (200 ml)

Sources & evidence

ORD record
ord-4e4b676903c84e078133a0ede3be0187
Source dataset
uspto-grants-1984_12
Patent number
US04490374

Reaction notes

Loading…