Potassium Carbonate → (R)-cyclohexyl-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid methyl ester

HRID 388449Notes

Reaction equation

HRID 388449 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[N:5]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]1=[O:16].[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+]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[N:5]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([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:6]1=[O:16]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 17836486((1,4-Dimethylindole-3-yl)methyl)trimethylammonium iodideHCID 68728019(R)-cyclohexyl-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid methyl ester

Product 1

HCID 68743060(R)-cyclohexyl-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid methyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (R)-cyclohexyl-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid methyl ester (100 mg, 0.32 mmol) and (1,4-dimethyl-1H-indol-3-ylmethyl)-trimethylammonium iodide (160 mg, 0.47 mmol) in DMF (2.5 mL) is added potassium carbonate (K2CO3) (100 mg, 0.72 mmol). The mixture is stirred at 60° C. for 4 hours. The reaction mixture is allowed to cool to room temperature, dilute with EtOAc (50 mL) and is washed with H2O (50 mL×3). The organic layer is dried over sodium sulfate and concentrated. The resulting residue is triturated with EtOAc and hexanes to afford (R)-cyclohexyl-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid methyl ester (124 mg, 94%).

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. concentrationconcentrated
  5. customThe resulting residue is triturated with EtOAc and hexanes

Sources & evidence

ORD record
ord-d6a57139cf2a45ac9008752872c27dfe
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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