Chloroacetone → 7-{[1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

HRID 1668668Notes

Reaction equation

HRID 1668668 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][CH:26]=[C:25]2[CH3:31].Cl[CH2:33][C:34](=[O:36])[CH3:35].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:34]([CH2:35][N:18]1[CH2:19][CH2:20][CH:15]([CH2:14][O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([O:21][C:22]4[CH:23]=[C:24]5[C:28](=[CH:29][CH:30]=4)[NH:27][CH:26]=[C:25]5[CH3:31])=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:2][CH3:1])[CH2:16][CH2:17]1)(=[O:36])[CH3:33]

Participants

5

Reactant 3

HCID 6571ChloroacetoneHCID 11430Potassium CarbonateHCID 220307946-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline

Product 1

HCID 112944517-{[1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline (0.2 g), chloroacetone (0.046 ml), potassium carbonate (0.1 g) and DMF (6 ml) was stirred and heated to 70° C. for 1 hour. The mixture was cooled to ambient temperature, the precipitate was removed by filtration, the solvent was removed by evaporation under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with dichloromethane and ending dichloromethane/methanol (93/7). Evaporation of the solvents gave a foam which was triturated under ether/pentane (70/30) to give a solid which was collected by filtration and dried under vacuum to give 7-{[1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (0.074 g).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe precipitate was removed by filtration
  3. customthe solvent was removed by evaporation under vacuum
  4. customthe residue was purified by column chromatography on silica using
  5. temperatureincreasingly polar solvent mixtures
  6. customEvaporation of the solvents
  7. customgave a foam which
  8. customwas triturated under ether/pentane (70/30)
  9. customto give a solid which
  10. filtrationwas collected by filtration
  11. customdried under vacuum

Sources & evidence

ORD record
ord-156f9e1ee05a47409a78fb22cc8e7633
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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