Cesium carbonate → 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-(1H-indazol-5-yloxy)-6-methoxyquinazoline

HRID 2068091Notes

Reaction equation

HRID 2068091 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].[OH:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][N:32]=[CH:31]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:27][C:28]4[CH:29]=[C:30]5[C:34](=[CH:35][CH:36]=4)[NH:33][N:32]=[CH:31]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 1014381H-Indazol-5-olHCID 589602297-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 101519827-[3-(4-acetylpiperazin-1-yl)propoxy]-4-(1H-indazol-5-yloxy)-6-methoxyquinazolineYield 43%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (235 mg, 0.62 mmol), (prepared as described for the starting material in Example 7), 5-hydroxyindazole (100 mg, 0.75 mmol) and cesium carbonate (303 mg, 0.93 mmol) in acetone (15 ml) was heated at reflux for 1.25 hours. The mixture was cooled, filtered and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4). The residue was further purified by preparative HPLC to give 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-(1H-indazol-5-yloxy)-6-methoxyquinazoline (127 mg, 43%) as a white foam.

Workup

  1. custom(prepared
  2. temperaturewas heated
  3. temperatureat reflux for 1.25 hours
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (saturated with ammonia) (96/4)
  9. customThe residue was further purified by preparative HPLC

Sources & evidence

ORD record
ord-2b15b1cd3fe44b1ba9bb97500bf8c2cd
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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