Potassium Carbonate → (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline

HRID 454273Notes

Reaction equation

HRID 454273 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][CH:17]=[C:16]4[CH3:22])=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:42][C@@H:43]2[O:45][CH2:44]2)(=O)=O)=CC=1>CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:42][C@H:43]1[CH2:44][O:45]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[C:16]2[CH3:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 154187Glycidyl tosylate, (R)-HCID 1357631157-Hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

Product 1

HCID 54069082(2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazolineYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (1.35 g, 4.2 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (1.74 g, 12.6 mmol) and (2R)-(−)-glycidyl tosylate (1.92 g, 8.4 mmol) in DMF (25 ml) was stirred at 60° C. for 2 hours and allowed to cool to ambient temperature. The reaction mixture was filtered and the solvent removed in vacuo. The residue was dissolved in dichloromethane and washed with saturated sodium hydrogen carbonate solution. The organic layer was then dried (MgSO4), filtered and solvent removed in vacuo to give a solid. This was triturated with ether and the solid filtered off and dried to give (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (842 mg, 53%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. customthe solvent removed in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with saturated sodium hydrogen carbonate solution
  7. dry with materialThe organic layer was then dried (MgSO4)
  8. filtrationfiltered
  9. customsolvent removed in vacuo
  10. customto give a solid
  11. customThis was triturated with ether
  12. filtrationthe solid filtered off
  13. customdried

Sources & evidence

ORD record
ord-a4ab46b7dbf34317aa5399bccfdf2f4e
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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