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

HRID 1517279ノート

反応式

HRID 1517279 の反応式
CS([O:5][CH2:6][C@@H:7]([O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1)[CH3:8])(=O)=O.CC(C)([O-])C.[K+].[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([O:39][C:40]4[N:45]=[CH:44][C:43](O)=[CH:42][CH:41]=4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[N:24]1.Cl>O.CS(C)=O>[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([O:39][C:40]4[CH:41]=[CH:42][C:43]([O:5][CH2:6][C@H:7]([O:9][CH:10]5[CH2:15][CH2:14][CH2:13][CH2:12][O:11]5)[CH3:8])=[CH:44][N:45]=4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[N:24]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 59627439(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl methanesulfonateHCID 684298776-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol

生成物 1

HCID 68429798N-(1-methyl-1H-pyrazol-3-yl)-6-[(5-{[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]oxy}pyridin-2-yl)oxy] quinazoline-4-amine収率 75.1%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl methanesulfonate (214 mg, 0.90 mmol) and potassium tert-butoxide (200 mg, 1.8 mmol) were added to a dimethyl sulfoxide solution (5 ml) of 6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol (300 mg, 0.90 mmol) obtained in Example 6-3), and the reaction solution was stirred for 24 hours at 100° C. The reaction solution was cooled to room temperature, then water and aqueous 1 N hydrochloric acid solution (0.9 ml, 0.9 mmol) were added, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=99:1) to obtain N-(1-methyl-1H-pyrazol-3-yl)-6-[(5-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]oxyl pyridin-2-yl)oxy]quinazoline-4-amine (322 mg, yield: 75%) as a pale brown solid.

後処理

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=99:1)

出典と根拠

ORDレコード
ord-78d76566c8a14d3dba356cf569561f91
出典データセット
uspto-grants-2012_07
特許番号
US08232284B2

反応ノート

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