Dimethylformamide → HCID 21717271, compound

HRID 1386288Notes

Reaction equation

HRID 1386288 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-].CN(C=O)C.[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][N:33]3[CH:37]=[CH:36][N:35]=[CH:34]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1>C1COCC1>[ClH:17].[N:33]1([CH2:32][CH2:31][O:30][C:24]2[CH:23]=[C:22]3[C:27]([C:18]([CH:3]4[C:4]5[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=5)[NH:1][C:2]4=[O:10])=[N:19][CH:20]=[N:21]3)=[CH:26][C:25]=2[O:28][CH3:29])[CH:37]=[CH:36][N:35]=[CH:34]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 166653HydrideHCID 321710OxindoleHCID 111412614-Chloro-6-methoxy-7-(2-(imidazol-1-yl)ethoxy)quinazoline

Product 1

HCID 21717271HCID 21717271, compoundYield 61.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of oxindole (164 mg, 1.23 mmol) in THF (3 ml) was added dropwise under nitrogen, to sodiun hydride (49 mg, 1.23 mmol, prewashed with hexane) in THF (3 ml). The mixture was stirred for 30 minutes at ambient temperature and DMF (2 ml) and then 4-chloro-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (125 mg, 0.41 mmol) was added. The mixture was heated at 60° C. for 30 minutes and the THF was removed by evaporation. The residue was partitioned between saturated aqueous ammonium chloride solution and ether. The organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. The solid was dissolved in methylene chloride (5 ml), methanol (0.5 ml) and isopropanol (3 ml) and SM isopropanolic hydrogen chloride (0.5 ml) was added. The mixture was concentrated by evaporation to 2 ml total volume and the resulting precipitated solid was collected by filtration, washed with isopropanol followed by ether and dried under vacuum to give 7-(2-(imidazol-1-yl)ethoxy)-6-methoxy4-(oxindol-3-yl)quinazoline hydrochloride (110 mg, 61%).

Workup

  1. temperatureThe mixture was heated at 60° C. for 30 minutes
  2. customthe THF was removed by evaporation
  3. customThe residue was partitioned between saturated aqueous ammonium chloride solution and ether
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. dissolutionThe solid was dissolved in methylene chloride (5 ml)
  8. additionmethanol (0.5 ml) and isopropanol (3 ml) and SM isopropanolic hydrogen chloride (0.5 ml) was added
  9. concentrationThe mixture was concentrated by evaporation to 2 ml total volume
  10. customthe resulting precipitated solid
  11. filtrationwas collected by filtration
  12. washwashed with isopropanol
  13. customdried under vacuum

Sources & evidence

ORD record
ord-ac6d14afbfcb4b1a9b94fc482a8587e1
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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