Dimethylformamide → 4-Chloro-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

HRID 495384Notes

Reaction equation

HRID 495384 reaction equation
[O:1]=[S:2]1(=[O:25])[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.S(Cl)([Cl:28])=O.CN(C=O)C>C1(C)C=CC=CC=1>[Cl:28][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][S:2](=[O:25])(=[O:1])[CH2:3][CH2:4]3)=[C:13]([O:23][CH3:24])[CH:14]=2)[N:19]=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1355941107-(3-(1,1-Dioxothiomorpholino)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one

Product 1

HCID 219360004-Chloro-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

After repetition of the previous reaction, a mixture of 7-[3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy]-6-methoxy-3,4-dihydroquinazolin-4-one (4.2 g), thionyl chloride (45 ml) and DMF (0.1 ml) was heated to reflux for 2.5 hours. The residue was diluted with toluene and was evaporated under vacuum. The residue was taken up in water and basified to pH 8 with a saturated aqueous sodium bicarbonate solution. The mixture was extracted with methylene chloride and the organic layer was washed in turn with water and brine. The organic solution was filtered through phase separating paper and evaporated to give an orange solid which was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. The resultant solid was triturated under diethyl ether and dried to give 4chloro-7-[3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy]-6-methoxyquinazoline (2.27 g); Mass Spectrum: M+H+ 386.

Workup

  1. customAfter repetition of the previous reaction
  2. temperaturewas heated
  3. temperatureto reflux for 2.5 hours
  4. customwas evaporated under vacuum
  5. extractionThe mixture was extracted with methylene chloride
  6. washthe organic layer was washed in turn with water and brine
  7. filtrationThe organic solution was filtered through phase
  8. customseparating paper
  9. customevaporated
  10. customto give an orange solid which
  11. customwas purified by column chromatography on silica using
  12. additiona 19:1 mixture of methylene chloride and methanol as eluent
  13. customThe resultant solid was triturated under diethyl ether
  14. customdried

Sources & evidence

ORD record
ord-8d1fdbe3b8494b9b80f6f3037981b7a8
Source dataset
uspto-grants-2005_09
Patent number
US06939866B2

Reaction notes

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