Ethanol → 3-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}propan-1-ol

HRID 1517263Notes

Reaction equation

HRID 1517263 reaction equation
C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C(O)C.[CH3:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[C:35]([O:38][C:39]4[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][CH2:48][O:49]C5CCCCO5)=[CH:41][N:40]=4)[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[N:23]1>O>[CH3:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[C:35]([O:38][C:39]4[N:40]=[CH:41][C:42]([O:45][CH2:46][CH2:47][CH2:48][OH:49])=[CH:43][CH:44]=4)[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[N:23]1

Participants

5

Reactant 3

HCID 702EthanolHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 68430647N-(1-methyl-1H-pyrazol-3-yl)-6-({5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)quinazoline-4-amine

Product 1

HCID 426112463-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}propan-1-olYield 69.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Pyridinium p-toluenesulfonate (243 mg, 0.97 mmol) was added to an ethanol solution (2 ml) of N-(1-methyl-1H-pyrazol-3-yl)-6-({5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)quinazoline-4-amine (230 mg, 0.48 mmol) obtained in the above reaction, and stirred under reflux for 2 hours. The reaction solution was cooled to room temperature, saline water was added, and extracted with chloroform/methanol (9:1), the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:5) to obtain 3-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}propan-1-ol (131 mg, yield: 69%) as a pale yellow amorphous solid.

Workup

  1. customobtained in the above reaction
  2. temperatureunder reflux for 2 hours
  3. extractionextracted with chloroform/methanol (9:1)
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:5)

Sources & evidence

ORD record
ord-ce081514bcef46d1a3e75a77e963f446
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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