Dimethylformamide → 199327-65-6

HRID 1386286Notes

Reaction equation

HRID 1386286 reaction equation
[N+: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])=[O:2].[H-].[Na+].[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.CN(C=O)C>C1COCC1>[ClH:16].[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH2:30][CH2:31][O:32][CH3:33])[N:20]=[CH:19][N:18]=[C:17]2[CH:7]1[C:6]2[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[NH:9][C:8]1=[O:13]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2303665-Nitro-2-oxindoleHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717255199327-65-6Yield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-nitrooxindole (400 mg, 2.2 mmol) in THF (4 ml) was added to sodium hydride (89 mg, 3.7 mmol, prewashed with THF) in THF (4 ml). The mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (200 mg, 0.75 mmol), (prepared as described for the starting material in Example 2), in THF (3 ml) and DMF (1 ml) was added dropwise. The mixture was stirred for 1 hour at ambient temperature, followed by 1.5 hours at 70° C. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH7 with 2M hydrochloric acid. The precipitated product was collected by filtration, washed with ether and dried under vacuum at 60° C. The solid was dissolved in methanol (10 ml) and 7.5M hydrogen chloride in methanol (2 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 6-methoxy-7-(2-methoxyethoxy)-4-(5-nitrooxindol-3-yl)quinazoline hydrochloride (173 mg, 57%).

Workup

  1. stirringThe mixture was stirred for 1 hour at ambient temperature
  2. waitfollowed by 1.5 hours at 70° C
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between ethyl acetate and water
  5. filtrationThe precipitated product was collected by filtration
  6. washwashed with ether
  7. customdried under vacuum at 60° C
  8. dissolutionThe solid was dissolved in methanol (10 ml)
  9. addition7.5M hydrogen chloride in methanol (2 ml) was added
  10. customThe volatiles were removed by evaporation
  11. customthe solid residue was triturated with ether
  12. filtrationcollected by filtration
  13. customdried under vacuum

Sources & evidence

ORD record
ord-e14f7b380bdb4693bc04bd1f25d39efe
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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