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

HRID 454168Notes

Reaction equation

HRID 454168 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.CN(C=O)C.S(Cl)([Cl:32])=O>>[Cl:32][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 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 53%

Procedure

6-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydro quinazolin-4-one (2.15 g, 6.48 mmol) was suspended in thionyl chloride (25 ml) and DMF (0.18 ml) and stirred under 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 with saturated with aqueous sodium hydrogen carbonate solution and the aqueous solution extracted 4 times with dichloromethane. The combined extracts were washed with water and brine then filtered through phase separating paper. The filtrate was evaporated under vacuum and the residue purified by silica column chromatography eluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1) to give a solid which was triturated with a little acetone, filtered and dried to give 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (1.2 g, 53%). This was used without further purification.

Workup

  1. temperatureunder reflux for 2 hours
  2. customThe thionyl chloride was evaporated under vacuum
  3. customthe residue azeotroped twice with toluene
  4. extractionthe aqueous solution extracted 4 times with dichloromethane
  5. washThe combined extracts were washed with water and brine
  6. filtrationthen filtered through phase
  7. customseparating paper
  8. customThe filtrate was evaporated under vacuum
  9. customthe residue purified by silica column chromatography
  10. washeluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1)
  11. customto give a solid which
  12. customwas triturated with a little acetone
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-750d639b10a4430d9cf9cf367a0c471d
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…