Dimethylformamide → Quinazoline

HRID 1386352Notes

Reaction equation

HRID 1386352 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[NH:3][CH:2]=1.CN(C=O)C>S(Cl)(Cl)=O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][CH:2]=1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 1354087534(1H)-Quinazolinone

Product 1

HCID 9210QuinazolineYield 293.9%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 6-methoxy-7-(2-(N-methyl-N-(3-morpholinopropylsulphonyl))amino)ethoxy)-3,4-dihydroquinazolin4-one (176 mg, 0.4 mmol) in thionyl chloride (4 ml) containing DMF (100 μl) was stirred at 45° C. for 1 hour. The volatiles were removed by evaporation and by azeotroping with toluene. The residue was partitioned between methylene chloride and water, the aqueous phase was adjusted to pH8 with saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methanol/methylene chloride (a gradient from 3/100 to 10/90). The purified product was triturated with ether, collected by filtration and dried under vacuum to give 4-chloro-6-methoxy-7-(2-(N-methyl-N-(3-morpholinopropylsulphonyl)]amino)ethoxy)quinazoline (153 mg, 71%).

Workup

  1. customThe volatiles were removed by evaporation
  2. customby azeotroping with toluene
  3. customThe residue was partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methanol/methylene chloride (a gradient from 3/100 to 10/90)
  10. customThe purified product was triturated with ether
  11. filtrationcollected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-2f4ab7fcc9d147b794cd39b4345af37b
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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