Potassium Carbonate → 4-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline

HRID 1791840Notes

Reaction equation

HRID 1791840 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:24][C:25]1[C:33]([OH:34])=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[C:28]([CH3:35])[NH:29]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:24][C:25]1[C:33]([O:34][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[C:28]([CH3:35])[NH:29]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 103520364-fluoro-2-methyl-1H-indol-5-olHCID 11088974HCID 11088974, compound

Product 1

HCID 101832934-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazolineYield 62.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 4-chloro-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (1.22 g, 3.65 mmol), (prepared as described for the starting material in Example 241), 4-fluoro-5-hydroxy-2-methylindole (723 mg, 4.38 mmol), (prepared as described for the starting material in Example 237), in DMF (20 ml) containing potassium carbonate (756 mg, 5.48 mmol) was stirred at 95° C. for 3 hours. After cooling, the mixture was filtered and the filtrate was evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1) followed by methylene chloride/methanol/methanol saturated with ammonia (90/5/5). The fractions containing the expected product were combined and evvaporated. The residue was triturated with ether, filtered, washed with ether and dried under vacuum. The solid was dissolved in methylene chloride/ethyl acetate and the minimum of methanol, filtered and the volatiles were removed under vacuum. The solid was triturated with ether, filtered, washed with ether and dried under vacuum at 50° C. to give 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (1.06 g, 62%).

Workup

  1. custom(prepared
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered
  4. customthe filtrate was evaporated
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (9/1)
  7. additionThe fractions containing the expected product
  8. customThe residue was triturated with ether
  9. filtrationfiltered
  10. washwashed with ether
  11. customdried under vacuum
  12. dissolutionThe solid was dissolved in methylene chloride/ethyl acetate
  13. filtrationthe minimum of methanol, filtered
  14. customthe volatiles were removed under vacuum
  15. customThe solid was triturated with ether
  16. filtrationfiltered
  17. washwashed with ether
  18. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-7fa8fae7a4d149c49ffe087d086ce4ad
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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