Dimethyl Sulfoxide → HCID 21717287, compound

HRID 1386354Notes

Reaction equation

HRID 1386354 reaction equation
[NH2:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3].[H-].[Na+].[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.CS(C)=O>CN(C=O)C>[ClH:17].[NH2:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH:8]2[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1)(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 101982322-Oxoindoline-5-sulfonamideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717287HCID 21717287, compoundYield 25.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 5-aminosulphonyloxindole (283 mg, 1.3 mmol), (prepared as described for the starting material in Example 60), in DMF (3.5 ml) was added dropwise to a suspension of sodium hydride (53 mg, 1.3 mmol, prewashed with hexane) in DMF (1.5 ml). The mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (150 mg, 0.44 mmol), (prepared as described for the starting material in Example 5), in DMF (4 ml) was added. The mixture was stirred for 20 minutes at 65° C., DMSO (2 ml) was added and heating was continued for 1 hour at 65° C. The mixture was allowed to cool, the volatiles were removed by evaporation and the residue was partitioned between ether and water. The aqueous layer was adjusted to pH7.8 with 1M hydrochloric acid and the resulting precipitate was collected by filtration, washed with water and ether, and dried under vacuum. The solid was dissolved in methanol/methylene chloride (1/1) and 2.2M ethereal hydrogen chloride (1 ml) was added. The mixture was stirred for 10 minutes at ambient temperature and the volatiles were removed by evaporation. The solid residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(5-aminosulphonyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (62 mg, 24%).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 20 minutes at 65° C.
  3. temperatureheating
  4. waitwas continued for 1 hour at 65° C
  5. temperatureto cool
  6. customthe volatiles were removed by evaporation
  7. customthe residue was partitioned between ether and water
  8. filtrationthe resulting precipitate was collected by filtration
  9. washwashed with water and ether
  10. customdried under vacuum
  11. dissolutionThe solid was dissolved in methanol/methylene chloride (1/1)
  12. addition2.2M ethereal hydrogen chloride (1 ml) was added
  13. stirringThe mixture was stirred for 10 minutes at ambient temperature
  14. customthe volatiles were removed by evaporation
  15. customThe solid residue was triturated with ether
  16. filtrationcollected by filtration
  17. washwashed with ether
  18. customdried under vacuum

Sources & evidence

ORD record
ord-fb3c70d47b694b66a19b30ab355a038c
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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