Diethyl Ether → HCID 21717238, compound

HRID 1386326Notes

Reaction equation

HRID 1386326 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2)(=[O:3])[CH3:2].[H-].[Na+].[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.CCOCC>CN(C=O)C.O.C(OCC)(=O)C>[ClH:16].[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH:7]2[C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 102196435-acetyl-2,3-dihydro-1H-indol-2-oneHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717238HCID 21717238, compoundYield 50.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-acetyloxindole (272 mg, 1.56 mmol), (EP 0155828 A2), in DMF (1.5 ml) was added dropwise to a suspension of sodium hydride (62 mg, 1.56 mmol, prewashed with hexane) in DMF (3 ml) and, the mixture stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (175 mg, 0.52 mmol), (prepared as described for the starting material in Example 5), was added and the mixture was heated at 50° C. for 1.5 hours. The mixture was poured into a mixture of ether (30 ml), ethyl acetate (30 ml) and water (50 ml). The aqueous layer was separated and adjusted to pH7.8 with 2M hydrochloric acid and extracted with methylene chloride. The organic extracts were washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (90/10). The purified solid was dissolved in methylene chloride/methanol and 7M ethanolic hydrogen chloride (1.5 ml) was added. The volatiles were removed by evaporation, the residue collected and dried under vacuum to give 4-(5-acetyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (135 mg, 48%).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 50° C. for 1.5 hours
  3. customThe aqueous layer was separated
  4. extractionextracted with methylene chloride
  5. washThe organic extracts were washed with water, brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methylene chloride/methanol (90/10)
  10. dissolutionThe purified solid was dissolved in methylene chloride/methanol
  11. addition7M ethanolic hydrogen chloride (1.5 ml) was added
  12. customThe volatiles were removed by evaporation
  13. customthe residue collected
  14. customdried under vacuum

Sources & evidence

ORD record
ord-7d7b58530b1c4eb4ba1586ac199df58a
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…