Potassium Carbonate → 4-(2,3-dimethylindol-5yloxy)-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline

HRID 1791663Notes

Reaction equation

HRID 1791663 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:30][C:31]1[NH:32][C:33]2[C:38]([C:39]=1[CH3:40])=[CH:37][C:36]([OH:41])=[CH:35][CH:34]=2>CN(C=O)C>[CH3:30][C:31]1[NH:32][C:33]2[C:38]([C:39]=1[CH3:40])=[CH:37][C:36]([O:41][C:2]1[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=1)=[CH:35][CH:34]=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 220306904-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolineHCID 220307882,3-Dimethyl-1H-indol-5-ol

Product 1

HCID 220308724-(2,3-dimethylindol-5yloxy)-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolineYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (360 mg, 1.00 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (215 mg, 1.56 mmol) and 2,3-dimethyl-5-hydroxyindole (177 mg, 1.10 mmol), (Arch. Pharm. 1972, 305, 159), in DMF (8.0 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The solvent was removed by evaporation and the residue purified by silica column chromatography eluting with methanol (2.5%) in dichloromethane. The resulting solid was recrystallised from tertbutyl methyl ether/acetonitrile, filtered and washed with diethyl ether to give 4-(2,3-dimethylindol-5yloxy)-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (201 mg, 42%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. customThe solvent was removed by evaporation
  4. customthe residue purified by silica column chromatography
  5. washeluting with methanol (2.5%) in dichloromethane
  6. customThe resulting solid was recrystallised from tertbutyl methyl ether/acetonitrile
  7. filtrationfiltered
  8. washwashed with diethyl ether

Sources & evidence

ORD record
ord-a947657169974ce492a4995d6fbad691
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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