p-Toluenesulfonic acid → 3-[4-(5,7-Dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-phenyl]-propionic acid ethyl ester

HRID 336703Notes

Reaction equation

HRID 336703 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[CH2:15]([O:17][C:18](=[O:29])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][CH:22]=1)[CH3:16].S(=O)(O)[O-].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>O.CN(C)C(=O)C>[CH2:15]([O:17][C:18](=[O:29])[CH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)=[CH:25][CH:26]=1)[CH3:16]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 12169276Ethyl 3-(4-formylphenyl)propanoateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 1363988553-[4-(5,7-Dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-phenyl]-propionic acid ethyl esterYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
155 °C

Procedure

To a round-bottomed flask were added 2-amino-4,6-dimethoxy-benzamide (0.161 g, 0.82 mmol), 3-(4-formyl-phenyl)-propionic acid ethyl ester (0.170 g, 0.82 mmol), sodium bisulfite (0.160 g, 0.902 mmol), p-toluenesulfonic acid (0.016 g, 0.082 mmol) and N,N-dimethylacetamide (10 mL). The reaction mixture was refluxed at 155° C. for 16 h before being cooled to room temperature. Water was added and the precipitated solid was filtered off and washed with water and methanol to obtain 3-[4-(5,7-dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-phenyl]-propionic acid ethyl ester (0.304 g, 97%). The compound 3-[4-(5,7-dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-phenyl]-propionic acid ethyl ester (0.304 g, 0.795 mmol) was taken up in a 1:1 mixture of THF and methanol (6 mL). A solution of potassium hydroxide (0.089 g, 1.59 mmol) in water (6 mL) was added to the reaction mixture and stirred at room temperature for 16 h. The solvent was removed and the reaction mixture was acidified with 1 N hydrochloric acid. The precipitated solid was filtered off and washed with water and methanol. The solid was further washed with methanol to obtain 3-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)propanoic acid (0.143 g, 51%). Selected data: MS (ES) m/z: 355.0; MP 250.6-251.1° C.

Workup

  1. temperaturebefore being cooled to room temperature
  2. filtrationthe precipitated solid was filtered off
  3. washwashed with water and methanol

Sources & evidence

ORD record
ord-fab883717b2d434fb2201de619719a80
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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