2-Chloroaniline → 3-(2-Chlorophenyl)-2-(2-ethylcarbamoylethyl)-5,7-dimethyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic Acid Ethyl Ester

HRID 1039366Notes

Reaction equation

HRID 1039366 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:32])=[C:8]2[C:13](=[CH:14][C:15]=1[CH3:16])[N:12]=[C:11]([CH2:17][CH2:18][C:19]([O:21]CC)=O)[N:10]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:9]2=[O:31])=[O:5])[CH3:2].C(OC(=O)C1C(C)=C[C:43]([NH:47]C(=O)CCC(OCC)=O)=[C:39](C(O)=O)C=1C)C.ClC1C=CC=CC=1N.P(Cl)(Cl)Cl.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:32])=[C:8]2[C:13](=[CH:14][C:15]=1[CH3:16])[N:12]=[C:11]([CH2:17][CH2:18][C:19](=[O:21])[NH:47][CH2:43][CH3:39])[N:10]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:9]2=[O:31])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 72402-ChloroanilineHCID 24387Phosphorus trichlorideHCID 516892Sodium BicarbonateHCID 671755223-(2-Chlorophenyl)-2-(2-ethoxycarbonylethyl)-5,7-dimethyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid ethyl esterHCID 865975834-(3-Ethoxycarbonylpropionylamino)-2,6-dimethylisophthalic acid 1-ethyl ester

Product 1

HCID 115906083-(2-Chlorophenyl)-2-(2-ethylcarbamoylethyl)-5,7-dimethyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic Acid Ethyl Ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

3-(2-Chlorophenyl)-2-(2-ethoxycarbonylethyl)-5,7-dimethyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid ethyl ester: A stirred mixture of 4-(3-ethoxycarbonylpropionylamino)-2,6-dimethylisophthalic acid 1-ethyl ester (0.327 g, 0.89 mmol), 2-chloroaniline (0.28 mL, 2.66 mmol) and phosphorus trichloride (0.74 g, 5.4 mmol) in toluene (6 mL) is heated at 130° C. for 3 h. Upon cooling to room temperature, the reaction mixture is poured onto saturated sodium hydrogen carbonate solution and extracted with chloroform. The chloroform extracts are combined, washed with brine and dried over anhydrous MgSO4. The solvent is removed under reduced pressure and the residue is purified by flash chromatography over silica gel (initial eluent: 19:1 cyclohexane:ethyl acetate; final eluent: 7:3 cyclohexane:ethyl acetate) to afford the title compound.

Workup

  1. temperatureUpon cooling to room temperature
  2. extractionextracted with chloroform
  3. washwashed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. customThe solvent is removed under reduced pressure
  6. customthe residue is purified by flash chromatography over silica gel (initial eluent: 19:1 cyclohexane:ethyl acetate; final eluent: 7:3 cyclohexane:ethyl acetate)

Sources & evidence

ORD record
ord-00f1168618d54f7ea38050658f656957
Source dataset
uspto-grants-2013_10
Patent number
US08552015B2

Reaction notes

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