Potassium Carbonate → 7-[3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline

HRID 916476Notes

Reaction equation

HRID 916476 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]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][F:26])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[OH:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38]([CH3:43])=[CH:37]2>CC(N(C)C)=O>[F:26][CH2:25][CH2:24][N:21]1[CH2:22][CH2:23][N:18]([CH2:17][CH2:16][CH2:15][O:14][C:8]2[CH:7]=[C:6]3[C:11]([C:2]([O:33][C:34]4[CH:35]=[C:36]5[C:40](=[CH:41][CH:42]=4)[NH:39][C:38]([CH3:43])=[CH:37]5)=[N:3][CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 833362-methyl-1H-indol-5-olHCID 86597574HCID 86597574, compound

Product 1

HCID 102390807-[3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazolineYield 48.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 4-chloro-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline (240 mg, 0.63 mmol) in DMA (5 ml) was treated with potassium carbonate (96 mg, 0.69 mmol) and 5-hydroxy-2-methylindole (102 mg, 0.69 mmol), (WO 00/47212, Example 48), and stirred at 85° C. for 4 hours. The mixture was cooled and the solvent evaporated under vacuum to give a residue which was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (92/8). Evaporation of the relevant fractions gave an oil which crystallised on trituration with ether to give 7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline (150 mg, 48%).

Workup

  1. temperatureThe mixture was cooled
  2. customthe solvent evaporated under vacuum
  3. customto give a residue which
  4. customwas purified by column chromatography
  5. washeluting with methylene chloride/methanol (saturated with ammonia) (92/8)
  6. customEvaporation of the relevant fractions
  7. customgave an oil which
  8. customcrystallised on trituration with ether

Sources & evidence

ORD record
ord-a6d2b5ba66df4f7f8f174e6e161e3567
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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