Potassium Carbonate → 4-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(1-methylimidazol-2-ylmethoxy)quinazoline hydrochloride

HRID 279503

Reaction equation

HRID 279503 reaction equation
Cl.C([O:5][C:6]1[CH:7]=[C:8]([CH:23]=[CH:24][C:25]=1[CH3:26])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([OH:22])=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1)(=O)C.Cl.[Cl:28][CH2:29][C:30]1[N:31]([CH3:35])[CH:32]=[CH:33][N:34]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[ClH:28].[OH:5][C:6]1[CH:7]=[C:8]([CH:23]=[CH:24][C:25]=1[CH3:26])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH2:29][C:30]3[N:31]([CH3:35])[CH:32]=[CH:33][N:34]=3)=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27954062-(chloromethyl)-1-methyl-1H-imidazole hydrochlorideHCID 1356711804-(3-Acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 226248944-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(1-methylimidazol-2-ylmethoxy)quinazoline hydrochlorideYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 4-(3-acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (400 mg, 1.06 mmol), (prepared as described for the starting material in Example 1), 2-chloromethyl-1-methylimidazole hydrochloride (354 mg, 2.12 mmol), and potassium carbonate (585 mg) in DMF (15 ml) was heated at 60° C. for 15 hours. After cooling to ambient temperature the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was diluted with methanol (20 ml) and 2M sodium hydroxide (1 ml) was added. After stirring for 1 hour, the reaction mixture was diluted with water (20 ml) and 2M hydrochloric acid (3 ml) was added. The resulting solid was filtered off, washed with water and dried under vacuum to give 4-(3-hydroxy-4-methylanilino)-6-methoxy-7-(1-methylimidazol-2-ylmethoxy)quinazoline hydrochloride (150 mg, 29%).

Workup

  1. temperatureAfter cooling to ambient temperature the reaction mixture
  2. customwas partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. additionThe residue was diluted with methanol (20 ml) and 2M sodium hydroxide (1 ml)
  7. additionwas added
  8. additionthe reaction mixture was diluted with water (20 ml) and 2M hydrochloric acid (3 ml)
  9. additionwas added
  10. filtrationThe resulting solid was filtered off
  11. washwashed with water
  12. customdried under vacuum

Sources & evidence

ORD record
ord-0b4f777a31b34d89bbc79a7677a9906f
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Linked notes

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