Potassium Carbonate → Quinazoline

HRID 454025Notes

Reaction equation

HRID 454025 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8](OCC3CCN(CCS(C)(=O)=O)CC3)=[C:9](OC)[CH:10]=2)[N:5]=[CH:4][N:3]=1.OC1C=C2C(=CC=1)NC(C)=C2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:2]=[N:3][CH:4]=1

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 9210QuinazolineYield 164.6%

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)-7-41-(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-24fee55cdc414c76a709b19a952401d6
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…