Potassium Iodide → 4-(3-Acetoxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline

HRID 1384582

Reaction equation

HRID 1384582 reaction equation
Cl.[C:2]([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:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:36][C:37]1[N:41]([CH3:42])[C:40]2[CH:43]=[CH:44][CH:45]=[CH:46][C:39]=2[N:38]=1>CN(C=O)C>[C:2]([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]([O:22][CH2:36][C:37]3[N:41]([CH3:42])[C:40]4[CH:43]=[CH:44][CH:45]=[CH:46][C:39]=4[N:38]=3)=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1)(=[O:4])[CH3:3]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium Carbonate2×HCID 2480442-(Chloromethyl)-1-methylbenzimidazole2×HCID 1356711804-(3-Acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 226249724-(3-Acetoxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazolineYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-(3-acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (240 mg, 0.64 mmol), (prepared as described for the starting material in Example 1), potassium carbonate (310 mg, 2.25 mmol), potassium iodide (10 mg, 0.064 mmol) and 2-chloromethyl-1-methylbenzimidazole (153 mg, 0.7 mmol) in DMF (12 ml) was heated at 65° C. for 3 hours. Further 2-chloromethyl-1-methylbenzimidazole (90 mg, 0.41 mmol) and potassium carbonate (165 mg, 1.2 mmol) were added and heating continued for 2 hours. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with water and the solid product collected by filtration, washed with ether and dried under vacuum to give 4-(3-acetoxy-4-methylanilino)-6-methoxy-7-((1-methylbenzoimidazol-2-yl)methoxy)quinazoline (292 mg, 95%). MS-ESI: 506 [MNa]+

Workup

  1. custom(prepared
  2. temperatureheating
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with water and brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was triturated with water
  10. filtrationthe solid product collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-7974f7647296438298fdacb22346fb68
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Linked notes

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