Sodium hydride → HCID 21717232, compound

HRID 1386335Notes

Reaction equation

HRID 1386335 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])[NH2:2].[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>CN(C=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])[NH2:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 21717249HCID 21717249, compound

Product 1

HCID 21717232HCID 21717232, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-carbamoyloxindole (391 mg, 2.2 mmol) in DMF (5 ml) was added dropwise to sodium hydride (89 mg, 2.2 mmol, prewashed with hexane) in DMF (3.5 ml). The mixture was stirred for 20 minutes at ambient temperature and 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (250 mg, 0.74 mmol), (prepared as described for the starting material in Example 5), was added as a solid and the mixture was heated at 60° C. for 1 hour. The volatiles were removed by evaporation and the residue was partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH8.5 with 2M hydrochloric acid. The precipitate was collected by filtration, washed with water and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (2 ml) was added. The mixture was concentrated by evaporation and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(5-carbamoyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (184 mg, 45%).

Workup

  1. additionwas added as a solid
  2. temperaturethe mixture was heated at 60° C. for 1 hour
  3. customThe volatiles were removed by evaporation
  4. customthe residue was partitioned between ethyl acetate and water
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried under vacuum
  8. dissolutionThe solid was dissolved in methylene chloride/methanol
  9. addition3M ethereal hydrogen chloride (2 ml) was added
  10. concentrationThe mixture was concentrated by evaporation
  11. filtrationthe resulting precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-0eb5966e70ec4a1ea5adba392455f252
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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