Hydrochloric Acid → 4-(3-Hydroxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline hydrochloride

HRID 279565

Reaction equation

HRID 279565 reaction equation
[OH-].[Na+].C([O:6][C:7]1[CH:8]=[C:9]([CH:35]=[CH:36][C:37]=1[CH3:38])[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH2:24][C:25]3[N:29]([CH3:30])[C:28]4[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=4[N:26]=3)=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1)(=O)C.[ClH:39]>CO.C(Cl)Cl>[ClH:39].[OH:6][C:7]1[CH:8]=[C:9]([CH:35]=[CH:36][C:37]=1[CH3:38])[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH2:24][C:25]3[N:29]([CH3:30])[C:28]4[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=4[N:26]=3)=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 226249724-(3-Acetoxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline

Product 1

HCID 226250744-(3-Hydroxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline hydrochlorideYield 37%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

2M Aqueous sodium hydroxide solution (900 μl) was added to a solution of 4-(3 -acetoxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline (290 mg, 0.6 mmol) in methanol (15 ml) and methylene chloride (12 ml) and the mixture stirred for 25 minutes at ambient temperature. 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 solid residue was purified by column chromatography eluting with methylene chloride/methanol (97/3 and 95/5). The purified white solid was suspended in methanol (20 ml) and a solution of 7.5M hydrochloric acid in methanol (2 equivalents) was added. The solid was collected by filtration, washed with methanol and then pentane and dried under vacuum at 50° C. to give 4-(3-hydroxy-4-methylanilino)-6-methoxy-7-((1-methylbenzimidazol-2-yl)methoxy)quinazoline hydrochloride (106 mg, 37%).

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe solid residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (97/3 and 95/5)
  9. filtrationThe solid was collected by filtration
  10. washwashed with methanol
  11. dry with materialpentane and dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-8dade10479fe495f93acf6e657c5a977
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Linked notes

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