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

HRID 22773Notes

Reaction equation

HRID 22773 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][N:20]([CH3:23])[CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:27])=O>CN(C=O)C>[Cl:27][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][N:20]([CH3:23])[CH2:19][CH2:18]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 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)quinazoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

After repetition of the previous reaction, a mixture of 6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]-3,4-dihydroquinazoline-4-one (2.15 g), thionyl chloride (25 ml) and DMF (0.18 ml) was stirred and heated to reflux for 2 hours. The thionyl chloride was evaporated under vacuum and the residue azeotroped twice with toluene. The residue was taken up in water, basified by the addition of a saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (4 times). The combined extracts were washed in turn with water and brine and filtered through phase separating paper. The filtrate was evaporated under vacuum and the residue was purified by column chromatography on silica using a 100:8:1 mixture of methylene chloride, methanol and a concentrated aqueous ammonium hydroxide solution (0.880 g/ml) as eluent. The solid so obtained was triturated under acetone, filtered and dried to give 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline (1.2 g); Mass Spectrum: M+H+ 351.

Workup

  1. customAfter repetition of the previous reaction
  2. temperatureheated
  3. temperatureto reflux for 2 hours
  4. customThe thionyl chloride was evaporated under vacuum
  5. customthe residue azeotroped twice with toluene
  6. additionbasified by the addition of a saturated aqueous sodium bicarbonate solution
  7. extractionextracted with methylene chloride (4 times)
  8. washThe combined extracts were washed in turn with water and brine
  9. filtrationfiltered through phase
  10. customseparating paper
  11. customThe filtrate was evaporated under vacuum
  12. customthe residue was purified by column chromatography on silica using
  13. additiona 100:8:1 mixture of methylene chloride, methanol
  14. customThe solid so obtained
  15. customwas triturated under acetone
  16. filtrationfiltered
  17. customdried

Sources & evidence

ORD record
ord-bb6e942e4d9e4cb89bf76a59acb7072c
Source dataset
uspto-grants-2005_02
Patent number
US06849625B2

Reaction notes

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