Tetrahydrofuran → HCID 21717210, compound

HRID 1386311Notes

Reaction equation

HRID 1386311 reaction equation
[C:1]([NH:4][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:3])[CH3:2].[H-].[Na+].C1COCC1.[Cl:22][C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:35][CH2:36][CH2:37][O:38][CH3:39])=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][N:24]=1>CN(C=O)C>[ClH:22].[C:1]([NH:4][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:23]1[C:32]2[C:27](=[CH:28][C:29]([O:35][CH2:36][CH2:37][O:38][CH3:39])=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][N:24]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazolineHCID 11206280N-(2-oxoindolin-5-yl)acetamide

Product 1

HCID 21717210HCID 21717210, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 5-acetamidooxindole (212 mg, 1.1 mmol), (Zh. Obshch. Khim 1956, 26, 2019-2022), in DMF (2 ml) was added dropwise to sodium hydride.(89 mg, 2.23 mmol, prewashed with THF) in DMF (2 ml). The mixture was stirred for 5 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (100 mg, 0.37 mmol), (prepared as described for the starting material in Example 2), in DMF (2 ml) was added. The mixture was stirred for 1.5 hours at ambient temperature, the solvent was removed by evaporation and the mixture was partitioned between methylene chloride and water. The aqueous layer was adjusted to pH7 with 2M hydrochloric acid. The organic layer was separated, dried (MgSO4) and the solvent was removed by evaporation. The residue was purified by chromatography eluting with methanol/methylene chloride (gradient from 5/95 to 15/85). The purified solid was dissolved in methylene chloride and 4M methanolic hydrogen chloride (4ml) was added. The volatiles were removed by evaporation, the solid residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 60° C. to give 4-(5-acetamidooxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (95 mg, 56%).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 1.5 hours at ambient temperature
  3. customthe solvent was removed by evaporation
  4. customthe mixture was partitioned between methylene chloride and water
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customthe solvent was removed by evaporation
  8. customThe residue was purified by chromatography
  9. washeluting with methanol/methylene chloride (gradient from 5/95 to 15/85)
  10. dissolutionThe purified solid was dissolved in methylene chloride
  11. addition4M methanolic hydrogen chloride (4ml) was added
  12. customThe volatiles were removed by evaporation
  13. customthe solid residue was triturated with ether
  14. filtrationcollected by filtration
  15. washwashed with ether
  16. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-2bb3d7f3712448fcaf73b6afa91b81fc
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…