Hydrochloric Acid → HCID 21717261, compound

HRID 1386270Notes

Reaction equation

HRID 1386270 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](C(OCC)OCC)[C:13](=[O:25])[CH:12]2[C:26]1[C:35]2[C:30](=[CH:31][C:32]([O:38][CH2:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][N:27]=1)C1C=CC=CC=1.C(O)(C(F)(F)F)=O.Cl.[OH-].[Na+]>CO.O>[OH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:25])[CH:12]2[C:26]1[C:35]2[C:30](=[CH:31][C:32]([O:38][CH2:39][CH2:40][CH2:41][N:42]3[CH2:43][CH2:44][O:45][CH2:46][CH2:47]3)=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][N:27]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 21717268HCID 21717268, compound

Product 1

HCID 21717261HCID 21717261, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 4-(5-benzyloxy-1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (240 mg, 0.38 mmol) and TFA (8 ml) was heated at reflux for 30 minutes. The TFA was removed by evaporation, the residue was triturated with ether, the solid was collected by filtration, washed with ether and dried under vacuum. The orange solid thus obtained was dissolved in a 1M hydrochloric acid solution (5 ml, 5 mmol) and heated at reflux for 40 minutes. After cooling, the reaction mixture was adjusted to pH2.3 with 6M sodium hydroxide and subjected to column chromatography on reverse phase silica gel (C18 10μ) with a gradient of methanol in water (30 to 100%) as eluent The fractions containing the compound were combined, the solution was adjusted to pH1.5 with concentrated hydrochloric acid and the solvents removed by evaporation The residue was triturated with methanol/ether, the solid was collected by filtration, washed with ether and dried under vacuum at 40° C. to give 4-(5-hydroxyoxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline as a hydrochloride salt (90 mg, 45%) as an orange solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. customThe TFA was removed by evaporation
  4. customthe residue was triturated with ether
  5. filtrationthe solid was collected by filtration
  6. washwashed with ether
  7. customdried under vacuum
  8. customThe orange solid thus obtained
  9. temperatureheated
  10. temperatureat reflux for 40 minutes
  11. temperatureAfter cooling
  12. additioncontaining the compound
  13. customthe solvents removed by evaporation The residue
  14. customwas triturated with methanol/ether
  15. filtrationthe solid was collected by filtration
  16. washwashed with ether
  17. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-1a8c0e647de847b594ad6b349eac9f48
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…