Potassium Carbonate → HCID 22030537, compound

HRID 1791769Notes

Reaction equation

HRID 1791769 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]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:25][C:26]1[C:34]([OH:35])=[CH:33][CH:32]=[C:31]2[C:27]=1[CH:28]=[CH:29][NH:30]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:25][C:26]1[C:34]([O:35][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:33][CH:32]=[C:31]2[C:27]=1[CH:28]=[CH:29][NH:30]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineHCID 220305534-fluoro-1H-indol-5-ol

Product 1

HCID 22030537HCID 22030537, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (232 mg, 0.662 mmol), (prepared as described for the starting material in Examples 176 or 244), and 4-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing potassium carbonate (137 mg, I mmol) was stirred at 95° C. for 3 hours. After cooling, the residue was poured onto water (12 ml) and extracted with ethyl acetate. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by reversed phase C18 column chromatography eluting with methanol/ammonium carbonate (2 g of ammonium carbonate/liter saturated with CO2) (60/40 followed by 70/30). The fractions containing the expected product were combined and evaporated. The residue was dissolved in ethyl acetate, dried (MgSO4) and the volatiles were removed under vacuum. The residue was triturated with ether, filtered and dried under vacuum to give 4-(4-fluoroindol-5-yloxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (130 mg, 42%).

Workup

  1. custom(prepared
  2. custom(prepared
  3. temperatureAfter cooling
  4. additionthe residue was poured onto water (12 ml)
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by reversed phase C18 column chromatography
  10. washeluting with methanol/ammonium carbonate (2 g of ammonium carbonate/liter saturated with CO2) (60/40 followed by 70/30)
  11. additionThe fractions containing the expected product
  12. customevaporated
  13. dissolutionThe residue was dissolved in ethyl acetate
  14. dry with materialdried (MgSO4)
  15. customthe volatiles were removed under vacuum
  16. customThe residue was triturated with ether
  17. filtrationfiltered
  18. customdried under vacuum

Sources & evidence

ORD record
ord-827aca2c99d04cc1a044b4a8bf2652ae
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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