Acetic acid 4-chlorocarbonyl-2,6-dimethyl-phenyl ester → Acetic acid 4-(5,7-dimethoxy-1-methyl-4-oxo-1,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenyl ester

HRID 336735Notes

Reaction equation

HRID 336735 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([NH:14][CH3:15])[C:4]=1[C:5]([NH2:7])=[O:6].Cl[C:17]([C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([O:26][C:27](=[O:29])[CH3:28])=[C:21]([CH3:30])[CH:20]=1)=O>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]2[C:4]=1[C:5](=[O:6])[N:7]=[C:17]([C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([O:26][C:27](=[O:29])[CH3:28])=[C:21]([CH3:30])[CH:20]=1)[N:14]2[CH3:15]

Participants

4

Reactant 2

HCID 18704177Acetic acid 4-chlorocarbonyl-2,6-dimethyl-phenyl esterHCID 666617532,4-Dimethoxy-6-methylamino-benzamide

Product 1

HCID 66661452Acetic acid 4-(5,7-dimethoxy-1-methyl-4-oxo-1,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 2,4-dimethoxy-6-methylamino-benzamide (0.28 g, 1.33 mmol) in pyridine (10 mL) was added to acetic acid 4-chlorocarbonyl-2,6-dimethyl-phenyl ester (1.1 eq.) and stirred at room temperature for 14 h. The solvent was removed and the reaction mixture was acidified with 1 N HCl and extracted with ethyl acetate. The solvent was removed and the crude was purified by silica gel column chromatography (40 g) employing 1% methanol in dichloromethane to give acetic acid 4-(5,7-dimethoxy-1-methyl-4-oxo-1,4-dihydro-quinazolin-2-yl)-2,6-dimethyl-phenyl ester (0.34 g, 67%). Acetic acid 4-(5,7-dimethoxy-1-methyl-4-oxo-1,4-dihydro-quinazolin-2-yl)-2,6-dimethyl-phenyl ester (0.34 g, 0.89 mmol) was dissolved in ethanol (5 mL), 5% aqueous NaOH solution (10 mL) was added dropwise and the mixture was stirred at room temperature for 1.5 h. The compound was extracted with ethyl acetate and washed with ether to give 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-1-methylquinazolin-4(1H-one (0.13 g, 43%). Selected data: MS (ES) m/z: 340.17; MP 188.5-189.1° C.

Workup

  1. customThe solvent was removed
  2. extractionextracted with ethyl acetate
  3. customThe solvent was removed
  4. customthe crude was purified by silica gel column chromatography (40 g)

Sources & evidence

ORD record
ord-4debad2991b34820a58a2919ea68bf29
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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