3'-Aminoacetophenone → HCID 68561753, compound

HRID 1592949Notes

Reaction equation

HRID 1592949 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([O:12][C:13](=[O:15])[CH3:14])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:18][C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([NH2:27])[CH:22]=1)=[O:20]>C(O)(C)C>[ClH:1].[C:19]([C:21]1[CH:22]=[C:23]([NH:27][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([O:12][C:13](=[O:15])[CH3:14])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH:24]=[CH:25][CH:26]=1)(=[O:20])[CH3:18]

Participants

4

Reactant 2

HCID 74173'-AminoacetophenoneHCID 220221604-Chloro-7-methoxyquinazolin-6-yl acetate

Product 1

HCID 68561753HCID 68561753, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution (200 mL) of acetic acid 4-chloro-7-methoxy-6-quinazolinyl ester [described in U.S. Pat. Nos. 5,770,599 and 5,770,603] (3.74 g, 14.8 mmol) and 3-aminoacetophenone (2.0 g, 14.8 mmol) in isopropanol was heated under reflux for 5 hrs. After allowing to stand to cool, the precipitate was collected by filtration to give acetic acid 4-(3-acetylphenylamino)-7-methoxy-6-quinazolinyl ester hydrochloride (4.78 g, yield as monohydrochloride 83%). To a solution (100 mL) of this compound (3.0 g, 7.74 mmol) in methanol was added 28% aqueous ammonia (2 mL), and the mixture was stirred at room temperature for 4 hrs and then refluxed. The produced precipitate was collected by filtration and dried under reduced pressure to give 1-[3-(6-hydroxy-7-methoxy-4-quinazolinylamino)phenyl]ethanone (2.07 g, 87%). 2) A solution (20 mL) of 1-[3-(6-hydroxy-7-methoxy-4-quinazolinylamino)phenyl]ethanone (870 mg, 2.8 mmol) and pyridine (0.34 mL, 4.2 mmol) in acetonitrile was stirred on an ice bath and trifluoromethanesulfonic acid anhydride (0.57 mL, 3.4 mmol) was added dropwise. The reaction solution was gradually warmed up to room temperature and, after stirring at room temperature for 2 hrs, the mixture was concentrated. Aqueous sodium hydrogen carbonate was added to the residue and the mixture was stirred at room temperature for 30 min. The product was filtered and dried under reduced pressure to give the title compound 6a (1.20 g, 98%).

Workup

  1. temperatureunder reflux for 5 hrs
  2. temperatureto cool
  3. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-898a6507e4e44f62b98a709cee93396c
Source dataset
uspto-grants-2007_11
Patent number
US07294629B2

Reaction notes

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