Ammonia → 4-(2,3-Dimethylindol-5-ylamino)-7-hydroxy-6-methoxyquinazoline

HRID 454110Notes

Reaction equation

HRID 454110 reaction equation
C([O-])=O.[NH4+].C([O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]([NH:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28]([CH3:33])=[C:27]4[CH3:34])=[N:18][CH:19]=[N:20]2)=[CH:15][C:14]=1[O:35][CH3:36])C1C=CC=CC=1.N>[Pd].CN(C=O)C.CO>[CH3:33][C:28]1[NH:29][C:30]2[C:26]([C:27]=1[CH3:34])=[CH:25][C:24]([NH:23][C:17]1[C:16]3[C:21](=[CH:22][C:13]([OH:12])=[C:14]([O:35][CH3:36])[CH:15]=3)[N:20]=[CH:19][N:18]=1)=[CH:32][CH:31]=2

Participants

7

Reactant 3

HCID 222AmmoniaHCID 2723923Ammonium formateHCID 220309397-Benzyloxy-4-(2,3-dimethylindol-5-ylamino)-6-methoxyquinazoline

Product 1

HCID 1357631094-(2,3-Dimethylindol-5-ylamino)-7-hydroxy-6-methoxyquinazolineYield 75%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ammonium formate (20 g, 326 mmol) and 10% palladium on carbon (1 g) were added to a solution of 7-benzyloxy-4-(2,3-dimethylindol-5-ylamino)-6-methoxyquinazoline (10 g, 22 mmol) in DMF (100 ml) and methanol (300 ml). After stirring for 3 hours at ambient temperature, aqueous ammonia (120 ml) was added. The precipitate was filtered, washed with water and dried under vacuum. The residue was triturated with ethyl acetate and ether and was filtered, dried under vacuum and purified by column chromatography eluting with methanol/methylene chloride (5/95 followed by 10/90) to give 4-(2,3-dimethylindol-5-ylamino)-7-hydroxy-6-methoxyquinazoline (5.5 g, 75%).

Workup

  1. filtrationThe precipitate was filtered
  2. washwashed with water
  3. customdried under vacuum
  4. customThe residue was triturated with ethyl acetate and ether
  5. filtrationwas filtered
  6. customdried under vacuum
  7. custompurified by column chromatography
  8. washeluting with methanol/methylene chloride (5/95 followed by 10/90)

Sources & evidence

ORD record
ord-fab74b57751341baaf758f5d1bc67617
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…