Potassium Iodide → 4-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(2-methylthiazol-4-ylmethoxy) quinazoline hydrochloride

HRID 279504Notes

Reaction equation

HRID 279504 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]=[C:32]([CH3:35])[S:33][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[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]=[C:32]([CH3:35])[S:33][CH:34]=3)=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 1356711804-(3-Acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 226248954-(3-Hydroxy-4-methylanilino)-6-methoxy-7-(2-methylthiazol-4-ylmethoxy) quinazoline hydrochlorideYield 63.6%

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), 4-chloromethyl-2-methylthiazole hydrochloride (390 mg, 2.12 mmol), potassium carbonate (438 mg) and potassium iodide (40 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 (10 ml) and 2M sodium hydroxide (2 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-(2-methylthiazol4-ylmethoxy)quinazoline hydrochloride (300 mg, 59%).

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 (10 ml) and 2M sodium hydroxide (2 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-5504085b8aa5448eb945781d701462c1
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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