Ammonium formate → 7-Hydroxy-4-(indol-5-ylamino)-6-methoxyquinazoline

HRID 454198Notes

Reaction equation

HRID 454198 reaction equation
Cl.C([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[NH:26][CH:25]=[CH:24]4)=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:30][CH3:31])C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.CN(C=O)C.[Pd]>[OH:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[NH:26][CH:25]=[CH:24]4)=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:30][CH3:31]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 220305477-Benzyloxy-4(indol-5-ylamino)-6-methoxyquinazoline hydrochloride

Product 1

HCID 1357631067-Hydroxy-4-(indol-5-ylamino)-6-methoxyquinazolineYield 97%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of give 7-benzyloxy-4-(indol-5-ylamino)-6-methoxyquinazoline hydrochloride (10 g, 23.1 mmol) in methanol (300 ml) and DMF (100 ml) containing ammonium formate (22 gr, 347 mmol) and 10% palladium on charcoal (1 g) was stirred overnight at ambient temperature. The solution was filtered over celite and washed with DMF followed by methanol. The filtrate was evaporated. The residue was dissolved in aqueous ammonia 2 mM (300 ml) and stirred for 15 minutes. The solid was filtered, washed with water followed by ethyl acetate and ether and dried under vacuum at 50° C. for 2 days. The solid was purified by column chromatography eluting with methanol/methylene chloride (1/9). The volatiles were removed under vacuum and the solid was left under vacuum at 70° C. for 2 days to give 7-hydroxy-4-(indol-5-ylamino)-6-methoxyquinazoline (6.8 g, 97%)

Workup

  1. filtrationThe solution was filtered over celite
  2. washwashed with DMF
  3. customThe filtrate was evaporated
  4. dissolutionThe residue was dissolved in aqueous ammonia 2 mM (300 ml)
  5. stirringstirred for 15 minutes
  6. filtrationThe solid was filtered
  7. washwashed with water
  8. customdried under vacuum at 50° C. for 2 days
  9. customThe solid was purified by column chromatography
  10. washeluting with methanol/methylene chloride (1/9)
  11. customThe volatiles were removed under vacuum
  12. waitthe solid was left under vacuum at 70° C. for 2 days

Sources & evidence

ORD record
ord-cdabee17add045c68e3d937fadb57e56
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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