Potassium Carbonate → HCID 22030819, compound

HRID 454225Notes

Reaction equation

HRID 454225 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]=[CH:28][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]=[CH:28][NH:29]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11088974HCID 11088974, compoundHCID 220305534-fluoro-1H-indol-5-ol

Product 1

HCID 22030819HCID 22030819, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-chloro-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (300 mg, 0.9 mmol) and 4-fluoro-5-hydroxyindole (162 mg, 1 mmol), (prepared as described for the starting material in Example 242), in DMF (4.5 ml) containing potassium carbonate (185 mg, 1.3 mmol) was stirred at 90° C. for 1 hour. After cooling, the mixture was filtered and the solid was washed with DMF. The filtrate was evaporated and the residue was purified by column chromatography, eluting with methylene chloride followed by methanol/methylene chloride (1/99) followed by methanol saturated with ammonia/methylene chloride (2/98). The fractions containing the expected product were combined and evaporated. The solid was triturated with ether, filtered, washed with ether and dried under vacuum to give 4-(4-fluoroindol-5-yloxy)-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (282 mg, 69%).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. washthe solid was washed with DMF
  4. customThe filtrate was evaporated
  5. customthe residue was purified by column chromatography
  6. washeluting with methylene chloride
  7. additionThe fractions containing the expected product
  8. customevaporated
  9. customThe solid was triturated with ether
  10. filtrationfiltered
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-50d95059b3a54c3997975c77fcabe103
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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