Ammonium formate → 4-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

HRID 2068045Notes

Reaction equation

HRID 2068045 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[C:21]([F:30])=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][C:24]([CH3:29])=[CH:23]4)=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:31][CH3:32])C1C=CC=CC=1.C([O-])=O.[NH4+]>CN(C=O)C.[Pd].C(OCC)(=O)C>[F:30][C:21]1[C:20]([O:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:31][CH3:32])[CH:11]=3)[N:16]=[CH:15][N:14]=2)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[C:24]([CH3:29])[NH:25]2

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 101512047-(Benzyloxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazoline

Product 1

HCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-olYield 100%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 7-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (8.2 g, 19.1 mmol), ammonium formate (12 g, 190 mmol) in DMF (50 ml) containing 10% palladium on carbon (2 g) was stirred at ambient temperature for 1.5 hours. The mixture was diluted with ethyl acetate and filtered over diatomaceous earth. A solid precipitated out of the filtrate. The solid was filtered off. The filtrate was washed with aqueous sodium hydrogen carbonate, followed by brine and dried over magnesium sulphate. The volatiles were removed under vacuum. The residual solid was combined with the solid previously isolated from the filtrate and was then triturated with acetonitrile under cooling. The precipitate was filtered, washed with acetonitrile followed by diethyl ether and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (6.48 g, quant.).

Workup

  1. filtrationfiltered over diatomaceous earth
  2. customA solid precipitated out of the filtrate
  3. filtrationThe solid was filtered off
  4. washThe filtrate was washed with aqueous sodium hydrogen carbonate
  5. dry with materialdried over magnesium sulphate
  6. customThe volatiles were removed under vacuum
  7. custompreviously isolated from the filtrate
  8. customwas then triturated with acetonitrile
  9. temperatureunder cooling
  10. filtrationThe precipitate was filtered
  11. washwashed with acetonitrile
  12. customdried under vacuum

Sources & evidence

ORD record
ord-62296790f3a04e46a192ad7110227d94
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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