Potassium Carbonate → HCID 10160187, compound

HRID 454242Notes

Reaction equation

HRID 454242 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[CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:23][C:24]1[C:32]([OH:33])=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[CH:27][NH:28]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:23][C:24]1[C:32]([O:33][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[CH:27][NH:28]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 111417924-Chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolineHCID 220305534-fluoro-1H-indol-5-ol

Product 1

HCID 10160187HCID 10160187, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (1.76 g, 5.47 mmol), (prepared as described for the starting material in Example 9), 4-fluoro-5-hydroxyindole (0.992 g, 6.57 mmol), (prepared as described for the starting material in Example 242), in DMF (25 ml) containing potassium carbonate (1.14 g; 8.21 mmol) was heated at 95° C. for 1 hour. After cooling, the mixture was filtered and washed with DMF. The filtrate was evaporated and the residue was purified by column chromatography eluting with methanol/methylene chloride (1/9) followed by methanol/methanol chloride/methanol (containing ammonia) (16/80/4). The fractions containing the expected product were combined and evaporated. The residue was repurified by column chromatography eluting with a gradient of methylene chloride/methanol (80/20 to 40/60). The fractions containing the expected product were combined and evaporated. The residue was triturated in cold methanol and the solid was filtered, washed with ether and dried under vacuum to give 4-(4-fluoroindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (1.24 g, 52%).

Workup

  1. custom(prepared
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered
  4. washwashed with DMF
  5. customThe filtrate was evaporated
  6. customthe residue was purified by column chromatography
  7. washeluting with methanol/methylene chloride (1/9)
  8. additionThe fractions containing the expected product
  9. customevaporated
  10. customThe residue was repurified by column chromatography
  11. washeluting with a gradient of methylene chloride/methanol (80/20 to 40/60)
  12. additionThe fractions containing the expected product
  13. customevaporated
  14. customThe residue was triturated in cold methanol
  15. filtrationthe solid was filtered
  16. washwashed with ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-078a19dfbcf44f0580e1324da01f78c3
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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