Dimethylformamide → HCID 21717274, compound

HRID 1386294Notes

Reaction equation

HRID 1386294 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[H-].[Na+].[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1.CN(C=O)C>C1COCC1>[ClH:13].[CH3:25][O:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][C:20]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[N:17]=[CH:16][N:15]=[C:14]2[CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 321710OxindoleHCID 226249154-Chloro-6-methoxy-7-(4-pyridylmethoxy)quinazoline

Product 1

HCID 21717274HCID 21717274, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of oxindole (232 mg, 1.74 mmol) in THF (3 ml) was added dropwise under nitrogen, to sodium hydride (70 mg, 1.74 mmol, prewashed with hexane) in THF (3 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-6-methoxy-7-(4-pyridylmethoxy)quinazoline (175 mg, 0.58 mmol) and then DMF (2 ml) was added. The mixture was heated at 60° C. for 1 hour and the THF was removed by evaporation. The residue was partitioned between cooled 2M hydrochloric acid and ethyl acetate. The organic layer was extracted with 2M hydrochloric acid. The aqueous layers were combined, washed with ethyl acetate and ether, basified with aqueous sodium hydrogen carbonate and extracted with methylene chloride. The organic layer was washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (90/10 followed by 80/20 and 75/25). The purified solid product was dissolved in methanol/methylene chloride and SM methanolic hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation, the residue was resuspended in ether, collected by filtration, washed with ether and dried under vacuum to give 6-methoxy4-(oxindol-3-yl)-7-(4-pyridylmethoxy)quinazoline hydrochloride (50 mg, 21%).

Workup

  1. temperatureThe mixture was heated at 60° C. for 1 hour
  2. customthe THF was removed by evaporation
  3. customThe residue was partitioned
  4. temperaturebetween cooled 2M hydrochloric acid and ethyl acetate
  5. extractionThe organic layer was extracted with 2M hydrochloric acid
  6. washwashed with ethyl acetate and ether
  7. extractionextracted with methylene chloride
  8. washThe organic layer was washed with brine
  9. dry with materialdried (MgSO4)
  10. customthe solvent removed by evaporation
  11. customThe residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (90/10 followed by 80/20 and 75/25)
  12. dissolutionThe purified solid product was dissolved in methanol/methylene chloride
  13. additionSM methanolic hydrogen chloride (0.5 ml) was added
  14. customThe volatiles were removed by evaporation
  15. filtrationcollected by filtration
  16. washwashed with ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-fca7c910992e40ac84890336796ce02c
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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