Potassium Carbonate → HCID 10182393, compound

HRID 1791736Notes

Reaction equation

HRID 1791736 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]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]=[C:27]([CH3:34])[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][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]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]=[C:27]([CH3:34])[NH:28]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 103520364-fluoro-2-methyl-1H-indol-5-olHCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

Product 1

HCID 10182393HCID 10182393, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (2 gr, 6.22 mmol), (prepared as described for the starting material in Example 10), and 4-fluoro-5-hydroxy-2-methylindole (1.23 g, 7.46 mmol) in DMF (30 ml) containing potassium carbonate (1.28 g, 9.33 mmol) was stirred at 95° C. for 2 hours. After cooling, the volatiles were removed under vacuum and the residue was triturated with ether, filtered and dried under vacuum. The residue was purified by column chromatography eluting with methanol/methylene chloride (1/9) followed by methanol/methanol saturated with ammonia/methylene chloride (20/1/79 followed by 20/5/75). The fractions containing the expected product were combined and evaporated. The solid was triturated with methanol, filtered and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (1.95 g, 69%).

Workup

  1. temperatureAfter cooling
  2. customthe volatiles were removed under vacuum
  3. customthe residue was triturated with ether
  4. filtrationfiltered
  5. customdried under vacuum
  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 solid was triturated with methanol
  11. filtrationfiltered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-3050548ff5fe46a1810a9e01baa85851
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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