Cesium carbonate → 6-Benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

HRID 916369Notes

Reaction equation

HRID 916369 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][N:13]=[C:12]2Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[C:31]([OH:32])=[CH:30][CH:29]=[C:28]2[C:24]=1[CH:25]=[C:26]([CH3:33])[NH:27]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][N:13]=[C:12]2[O:32][C:31]1[C:23]([F:22])=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([CH3:33])=[CH:25]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 103520364-fluoro-2-methyl-1H-indol-5-olHCID 114265806-(Benzyloxy)-4-chloro-7-methoxyquinazoline

Product 1

HCID 666463136-Benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazolineYield 38.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-benzyloxy-4-chloro-7-methoxyquinazoline (0.39 g, 1.3 mmol), (EP1153920 production examples 28-30), 4-fluoro-5-hydroxy-2-methylindole (0.24 g, 1.43 mmol) and cesium carbonate (1.2 g, 4 mmol) in DMF (4 ml) was stirred at 95° C. for 45 minutes. After cooling, the mixture was filtered and the filtrate was evaporated under vacuum The residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and ethyl acetate to give 6-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline (0.213 g, 37%).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. customthe filtrate was evaporated under vacuum The residue
  4. customwas purified by column chromatography
  5. washeluting
  6. temperaturewith increasingly polar mixtures of methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-a2afab915d5d4541a23beb953c17a7f4
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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