Potassium Carbonate → 6-Methoxy-7-(1-methylpiperidin-4-ylmethoxy)-4-(2-trifluoromethylindol-5-yloxy)quinazoline

HRID 454048Notes

Reaction equation

HRID 454048 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.[OH:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([C:33]([F:36])([F:35])[F:34])=[CH:27]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)[N:5]=[CH:4][N:3]=[C:2]2[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([C:33]([F:36])([F:34])[F:35])=[CH:27]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolineHCID 220307102-(Trifluoromethyl)-1h-indol-5-ol

Product 1

HCID 220306286-Methoxy-7-(1-methylpiperidin-4-ylmethoxy)-4-(2-trifluoromethylindol-5-yloxy)quinazolineYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (50 mg, 0.155 mmol), (prepared as described for the starting material in Example 10), and 5-hydroxy-2-trifluoromethylindole (34 mg, 0.17 mmol) in DMF (1.5 ml) containing potassium carbonate (43 mg, 0.31 mmol) was heated at 90° C. for 2 hours. After cooling, the mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methanol/ethyl acetate/methylene chloride (10/50/40) followed by 2.5M ammonia in methanol/ethyl acetate/methylene chloride (10/50/40) to give 6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)-4-(2-trifluoromethylindol-5-yloxy)quinazoline (35 mg, 48%).

Workup

  1. custom(prepared
  2. temperatureAfter cooling
  3. customthe mixture was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe volatiles were removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methanol/ethyl acetate/methylene chloride (10/50/40)

Sources & evidence

ORD record
ord-ba0d8cbd430c4acda56f9cb4469dae21
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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