Ethyl Acetate → (S)-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-phenyl-acetic acid methyl ester

HRID 388460Notes

Reaction equation

HRID 388460 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([N:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]1=[O:22])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[I-].[CH3:25][N:26]1[C:34]2[C:29](=[C:30]([CH3:35])[CH:31]=[CH:32][CH:33]=2)[C:28]([CH2:36][N+](C)(C)C)=[CH:27]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C>[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([N:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH2:36][C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])[N:26]([CH3:25])[CH:27]=2)[C:12]1=[O:22])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 17836486((1,4-Dimethylindole-3-yl)methyl)trimethylammonium iodideHCID 68728966(S)-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl-acetic acid methyl ester

Product 1

HCID 68743824(S)-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-phenyl-acetic acid methyl esterYield 61.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (S)-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl-acetic acid methyl ester (110 mg, 0.35 mmol) and (1,4-dimethyl-1H-indol-3-ylmethyl)-trimethylammonium iodide (180 mg, 0.52 mmol) in DMF (2.5 mL) is added K2CO3 (150 mg, 1.09 mmol). The mixture is stirred at 60° C. for 4 hours. The reaction mixture is allowed to cool to room temperature, dilutes with EtOAc (50 mL) and is washed with H2O (50 mL×3). The organic layer is dried over sodium sulfate and is concentrated. The resulting residue is purified by flash chromatography with 50% EtOAc in hexanes as the eluent to afford (S)-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-phenyl-acetic acid methyl ester (100 mg, 60%).

Workup

  1. temperatureto cool to room temperature
  2. washis washed with H2O (50 mL×3)
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationis concentrated
  5. customThe resulting residue is purified by flash chromatography with 50% EtOAc in hexanes as the eluent

Sources & evidence

ORD record
ord-bd221fc3f49b48e680cf7c41024c18a9
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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