Cesium carbonate → 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline

HRID 2068049Notes

Reaction equation

HRID 2068049 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18](Cl)=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:27][C:28]1[C:36]([OH:37])=[CH:35][CH:34]=[C:33]2[C:29]=1[CH:30]=[C:31]([CH3:38])[NH:32]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18]([O:37][C:36]4[C:28]([F:27])=[C:29]5[C:33](=[CH:34][CH:35]=4)[NH:32][C:31]([CH3:38])=[CH:30]5)=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 103520364-fluoro-2-methyl-1H-indol-5-olHCID 589602297-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 112721357-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolineYield 77%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (20.0 g, 52.3 mmol), 4-fluoro-5-hydroxy-2-methylindole (10.5 g, 63.3 mmol), (prepared as described for the starting material in Example 1), and cesium carbonate (34.4 g, 106 mmol) in acetone (500 ml) was heated at reflux for 4 hours. The mixture was cooled and allowed to stand overnight. The mixture was filtered and the solid suspended in water and re-filtered and dried under vacuum. The solid was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (95/5) to give 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (20.4 g, 77%) as a white solid.

Workup

  1. custom(prepared
  2. temperaturewas heated
  3. temperatureat reflux for 4 hours
  4. temperatureThe mixture was cooled
  5. filtrationThe mixture was filtered
  6. filtrationre-filtered
  7. customdried under vacuum
  8. customThe solid was purified by column chromatography
  9. washeluting with methylene chloride/methanol (saturated with ammonia) (95/5)

Sources & evidence

ORD record
ord-6de255357edf47d794ac7f8d70c121a4
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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