Potassium Carbonate → 6-Methoxy-4-(2-methylindol-5-yloxy)-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazoline

HRID 1791560Notes

Reaction equation

HRID 1791560 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]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([CH3:38])=[CH:32]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]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH2:18][CH2:17]1)[N:5]=[CH:4][N:3]=[C:2]2[O:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([CH3:38])=[CH:32]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 833362-methyl-1H-indol-5-olHCID 220305344-Chloro-6-methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazoline

Product 1

HCID 220307596-Methoxy-4-(2-methylindol-5-yloxy)-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazolineYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-chloro-6-methoxy-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazoline (115 mg, 0.28 mmol), (prepared as described for the starting material in Example 12), 5-hydroxy-2-methylindole (50 mg, 0.33 mmol) and potassium carbonate (60 mg, 0.42 mmol) in DMF (1.5 ml) was stirred at 100° C. for 2 hours. After cooling, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by chromatography eluting with ethyl acetate/methylene chloride (1/1) followed by methanol/ethyl acetate/methylene chloride (1/4/5 and 1/0/9) to give 6-methoxy-4-(2-methylindol-5-yloxy)-7-((1-(2-methylsulphonylethyl)piperidin-4-yl)methoxy)quinazoline (60 mg, 41%).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by chromatography
  7. washeluting with ethyl acetate/methylene chloride (1/1)

Sources & evidence

ORD record
ord-00698d5f0e3b424b91f30a1c746a1b8d
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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