Dimethylformamide → 4-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

HRID 2233257Notes

Reaction equation

HRID 2233257 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]1)[N:9]=[CH:8][NH:7][C:6]2=O.CN(C)C=O.S(Cl)([Cl:30])=O>>[Cl:30][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1354703756-Methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4(3H)-one

Product 1

HCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolineYield 98%

Procedure

A solution of 6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)-3,4-dihydroquinazolin-4-one (2.8 g, 9.24 mmol) in thionyl chloride (28 ml) containing dimethylformamide (0.28 ml) was heated at reflux for 1 hour. The reaction was cooled, the volatiles were removed in vacuo and the resultant solid was triturated with diethyl ether, filtered, washed with diethyl ether and dried in vacuo. The solid was dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate, water and brine. Evaporation of the solvent and drying in vacuo yielded 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (2.9 g, 98% yield):

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe reaction was cooled
  4. customthe volatiles were removed in vacuo
  5. customthe resultant solid was triturated with diethyl ether
  6. filtrationfiltered
  7. washwashed with diethyl ether
  8. customdried in vacuo
  9. dissolutionThe solid was dissolved in dichloromethane
  10. washwashed with saturated aqueous sodium hydrogen carbonate, water and brine
  11. customEvaporation of the solvent
  12. customdrying in vacuo

Sources & evidence

ORD record
ord-ae26a1c027384922b4862cfe9fccecb6
Source dataset
uspto-grants-2010_05
Patent number
US07709479B1

Reaction notes

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