Dimethylacetamide → N-(1-methyl-1H-pyrazol-3-yl)-6-({5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)quinazoline-4-amine

HRID 1517262Notes

Reaction equation

HRID 1517262 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:4][N:3]=1.CC(C)([O-])C.[K+].CN(C)C(=O)C.[CH3:31][N:32]1[CH:36]=[CH:35][C:34]([NH:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([OH:48])[CH:46]=3)[N:41]=[CH:40][N:39]=2)=[N:33]1>O>[CH3:31][N:32]1[CH:36]=[CH:35][C:34]([NH:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([O:48][C:2]4[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][O:12][CH:13]5[CH2:18][CH2:17][CH2:16][CH2:15][O:14]5)=[CH:4][N:3]=4)[CH:46]=3)[N:41]=[CH:40][N:39]=2)=[N:33]1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 684276972-Fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridine

Product 1

HCID 68430647N-(1-methyl-1H-pyrazol-3-yl)-6-({5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)quinazoline-4-amineYield 97%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

2-Fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridine (305 mg, 1.10 mmol) and potassium tert-butoxide (140 mg, 1.24 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (120 mg, 0.50 mmol), and stirred at 180° C. for 14 hours under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, then saline water was added, and extracted with chloroform. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:3) to obtain N-(1-methyl-1H-pyrazol-3-yl)-6-({5-[3-(tetrahydro-2H-pyran-2-yloxy)prop oxy]pyridin-2-yl}oxy)quinazoline-4-amine (230 mg, yield: 97%) as a pale orange amorphous solid.

Workup

  1. temperatureThe reaction solution was cooled with ice
  2. extractionextracted with chloroform
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (Biotage, chloroform:methanol=100:3)

Sources & evidence

ORD record
ord-56b6c1c6e90b4042af90763711656fb8
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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