Hydrochloric Acid → 6-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydroquinazolin-4-one

HRID 454167Notes

Reaction equation

HRID 454167 reaction equation
ClC1C=CC([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=C(F)C=1.Cl.C(=O)([O-])O.[Na+]>>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1)[N:10]=[CH:9][NH:8][C:7]2=[O:6]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 218748154-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline

Product 1

HCID 1354581696-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydroquinazolin-4-oneYield 96.7%

Conditions

Temperature
95 °C

Procedure

4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (2.6 g, 5.6 mmol) was treated with 2.0 N aqueous hydrochloric acid (45 ml) and the mixture stirred at 95° C. for 2 hours. The mixture was cooled, basified by the addition of solid sodium hydrogen carbonate and the water removed by azeotroping with toluene. The residue was purified by silica column chromatography eluting with dichloromethane/methanol/0.880 aqueous ammonia (50/8/1) to give 6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydroquinazolin-4-one (1.8 g, 96%).

Workup

  1. temperatureThe mixture was cooled
  2. customthe water removed
  3. customby azeotroping with toluene
  4. customThe residue was purified by silica column chromatography
  5. washeluting with dichloromethane/methanol/0.880 aqueous ammonia (50/8/1)

Sources & evidence

ORD record
ord-603bfa2795da4a94a25dee47af526d1d
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…