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

HRID 577367Notes

Reaction equation

HRID 577367 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=O)C.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%

Conditions

Temperature
85 °C

Procedure

A solution of 6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)-3,4-dihydroquinazolin-4-one (2.8 g, 9.24 mmol) in thionyl chloride (28 ml) containing DMF (280 μl) was heated at reflux at 85° C. for 1 hour. After cooling, the volatiles were removed by evaporation. The precipitate was triturated with ether, filtered, washed with ether and dried under vacuum. The solid was dissolved in methylene chloride and saturated aqueous sodium hydrogen carbonate was added. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated to give 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (2.9 g, 98%).

Workup

  1. temperaturewas heated
  2. temperatureAfter cooling
  3. customthe volatiles were removed by evaporation
  4. customThe precipitate was triturated with ether
  5. filtrationfiltered
  6. washwashed with ether
  7. customdried under vacuum
  8. dissolutionThe solid was dissolved in methylene chloride
  9. additionsaturated aqueous sodium hydrogen carbonate was added
  10. customThe organic layer was separated
  11. washwashed with water, brine
  12. dry with materialdried (MgSO4)
  13. customevaporated

Sources & evidence

ORD record
ord-f2434dfedab2475292828a091413cdb0
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

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