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 81624ノート

反応式

HRID 81624 の反応式
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

参加物

6

反応物 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

生成物 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収率 97%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
180 °C

実験手順

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)propoxy]pyridin-2-yl}oxy)quinazoline-4-amine (230 mg, yield: 97%) as a pale orange amorphous solid.

後処理

  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)

出典と根拠

ORDレコード
ord-b3baefe2856a4e6b99abdfe631ed560f
出典データセット
uspto-grants-2014_09
特許番号
US08846700B2

反応ノート

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