Potassium Carbonate → HCID 58960243, compound

HRID 2068119Notes

Reaction equation

HRID 2068119 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([OH:24])=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:25])[NH:6]2.S(C1C=CC(C)=CC=1)(O[CH2:30][CH:31]1[O:33][CH2:32]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:30][C@H:31]4[CH2:32][O:33]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:25])[NH:6]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 160868Glycidyl tosylateHCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Product 1

HCID 58960243HCID 58960243, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4-(4-Fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (339 mg, 1 mmol), (prepared as described for the starting material in Example 7), was dissolved in dimethylacetamide (5 ml) under nitrogen. (2R) Glycidyl tosylate (285 mg, 1.25 mmol) and potassium carbonate (345 mg, 2.5 mmol) were added and the reaction stirred at ambient temperature for 2.5 hours, then warmed to 40° C. and left overnight. The solvent was removed under vacuum and the residue partitioned between water and dichloromethane. The organic phase was washed with brine and dried (Na2SO4). The residue was purified by column chromatography, eluting with methylene chloride/methanol (97/3) to give 4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[(2R)-oxiran-2-ylmethoxy]quinazoline (339 mg, 85%).

Workup

  1. temperaturewarmed to 40° C.
  2. waitleft overnight
  3. customThe solvent was removed under vacuum
  4. customthe residue partitioned between water and dichloromethane
  5. washThe organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (97/3)

Sources & evidence

ORD record
ord-67e455b1996a45479f97e1787e893bbe
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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