Sodium hydride → HCID 21717254, compound

HRID 1386342Notes

Reaction equation

HRID 1386342 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][NH:9][S:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][C:17](=[O:22])[CH2:16]3)(=[O:12])=[O:11])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:25][C:26]1[C:35]2[C:30](=[CH:31][C:32]([O:38][CH2:39][CH2:40][N:41]3[CH:45]=[CH:44][N:43]=[CH:42]3)=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][N:27]=1>CN(C=O)C>[ClH:25].[N:41]1([CH2:40][CH2:39][O:38][C:32]2[CH:31]=[C:30]3[C:35]([C:26]([CH:16]4[C:15]5[C:19](=[CH:20][CH:21]=[C:13]([S:10]([NH:9][CH2:8][CH2:7][N:4]6[CH2:5][CH2:6][O:1][CH2:2][CH2:3]6)(=[O:12])=[O:11])[CH:14]=5)[NH:18][C:17]4=[O:22])=[N:27][CH:28]=[N:29]3)=[CH:34][C:33]=2[O:36][CH3:37])[CH:45]=[CH:44][N:43]=[CH:42]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111412614-Chloro-6-methoxy-7-(2-(imidazol-1-yl)ethoxy)quinazolineHCID 217173035-(2-Morpholinoethylaminosulphonyl)oxindole

Product 1

HCID 21717254HCID 21717254, compoundYield 75.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-(2-morpholinoethylaminosulphonyl)oxindole (320 mg, 0.98 mmol), (prepared as described for the starting material in Example 48), in DMF (3.5 ml) was added to a suspension of sodium hydride (39.4 mg, 0.98 mmol, prewashed with THF) in DMF (1.5 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (100 mg, 0.32 mmol), (prepared as described for the starting material in Example 22), was added. The mixture was stirred for 1 hour at 60° C., allowed to cool and partitioned between methylene chloride and saturated aqueous ammonium chloride solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methanoymethylene chloride (5/95 to 15/85). The purified product was triturated with ether, collected by filtration and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 2.2M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the solid residue was triturated with ether, collected by filtration and dried under vacuum to give 7-(2-(imidazol-1-yl)ethoxy)-6-methoxy-4-(5-(2-morpholinoethylaminosulphonyl)oxindol-3-yl)quinazoline hydrochloride (153 mg, 64%).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 1 hour at 60° C.
  3. temperatureto cool
  4. custompartitioned between methylene chloride and saturated aqueous ammonium chloride solution
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified by column chromatography
  10. washeluting with methanoymethylene chloride (5/95 to 15/85)
  11. customThe purified product was triturated with ether
  12. filtrationcollected by filtration
  13. customdried under vacuum
  14. dissolutionThe solid was dissolved in methylene chloride/methanol
  15. addition2.2M ethereal hydrogen chloride (1 ml) was added
  16. customThe volatiles were removed by evaporation
  17. customthe solid residue was triturated with ether
  18. filtrationcollected by filtration
  19. customdried under vacuum

Sources & evidence

ORD record
ord-3802c058266c4fc88bd1ad045d71efd2
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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