Dimethylformamide → 4-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline

HRID 1791761Notes

Reaction equation

HRID 1791761 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:21]=[C:20]3[C:15]([C:16](=O)[NH:17][CH:18]=[N:19]3)=[CH:14][C:13]=2[O:23][CH3:24])[CH2:4][CH2:3]1.CN(C=O)C.S(Cl)([Cl:32])=O>>[Cl:32][C:16]1[C:15]2[C:20](=[CH:21][C:12]([O:11][CH2:10][CH2:9][CH2:8][N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[C:13]([O:23][CH3:24])[CH:14]=2)[N:19]=[CH:18][N:17]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1354581696-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineYield 68%

Conditions

Temperature
0 °C

Procedure

A solution of 7-(3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (22.6 g, 68 mmol) in thionyl chloride (300 ml) cotaining DMF (5 ml) was refluxed for 2 hours. After cooling, the volatiles were removed under vacuum and the residue was azeotroped with toluene twice. The solid was dissolved in methulene chloride and water was added. The mixture was cooled to 0° C. and the pH of the aqueous layer was adjusted to 7 with solid hydrogen carbonate and then raised to 10 with 6N Sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layer was washed with brine, dried (MgSO4), filtered and the volatiles were removed under vacuum. The residue was triturated with ether, filtered, washed with ether and dried under vacuum to give 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (16.3 gr, 68%).

Workup

  1. temperaturewas refluxed for 2 hours
  2. temperatureAfter cooling
  3. customthe volatiles were removed under vacuum
  4. customthe residue was azeotroped with toluene twice
  5. dissolutionThe solid was dissolved in methulene chloride
  6. additionwater was added
  7. temperatureraised to 10 with 6N Sodium hydroxide
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with methylene chloride
  10. washThe organic layer was washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customthe volatiles were removed under vacuum
  14. customThe residue was triturated with ether
  15. filtrationfiltered
  16. washwashed with ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-dab3f9c43bc744b18a88b00b23977c4f
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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