Dimethylformamide → 4-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazoline

HRID 454067

Reaction equation

HRID 454067 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][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.CN(C=O)C.S(Cl)([Cl:31])=O>>[Cl:31][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]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 1354715536-Methoxy-7-(3-piperidinopropoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 110021914-Chloro-6-methoxy-7-(3-(piperidin-1-YL)propoxy)quinazolineYield 76%

Procedure

A solution of 6-methoxy-7-(3-piperidinopropoxy)-3,4-dihydroquinazolin-4-one (1.5 g, 4.7 mmol) in thionyl chloride (15 ml) containing DMF (1.5 ml) was heated at reflux for 3 hours. After cooling, the volatiles were removed under vacuum. The residue was azeotroped with toluene. The solid was partitioned between methylene chloride and sodium hydrogen carbonate. The aqueous layer was adjusted to pH10 with 6M aqueous sodium hydroxide. The organic layer was separated, washed with brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography to give 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (1.21 g, 76%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. temperatureAfter cooling
  4. customthe volatiles were removed under vacuum
  5. customThe residue was azeotroped with toluene
  6. customThe solid was partitioned between methylene chloride and sodium hydrogen carbonate
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. customthe volatiles were removed by evaporation
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f166a99e3e2c40ca95a00b88db32b65a
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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