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Tetrahydrofuran → 3-(3-(4-(Thiazol-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 1694011
ノート
印刷プレビュー

反応式

HRID 1694011 の反応式
[NH2:1][C:2]1[C:7]([C:8]2[O:12][N:11]=[C:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.O1CCCC1.[OH-].[Na+].Cl[CH2:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1>CN(C)C=O>[S:31]1[CH:32]=[CH:33][N:34]=[C:30]1[CH2:29][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:10]2[CH:9]=[C:8]([C:7]3[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=3)[O:12][N:11]=2)=[CH:15][CH:16]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 140908642-(Chloromethyl)-1,3-thiazoleHCID 251143864-(5-(2-Amino-pyridin-3-yl)isoxazol-3-ylmethyl)phenol

生成物 1

HCID 592551823-(3-(4-(Thiazol-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine収率 78%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒
2 回

反応条件

温度
60 °C

実験手順

To 4-(5-(2-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (50.0 mg, 0.19 mmol) described in Manufacturing Example 5-1-1 were added tetrahydrofuran (3 mL) and a 5N aqueous sodium hydroxide solution (37.3 μL, 0.19 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction mixture was then concentrated under a reduced pressure to obtain a white solid. An N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-thiazole (29.8 mg, 0.22 mmol) described in Manufacturing Example 88-1-2 was added to a suspension of this solid and N,N-dimethylformamide (2 mL), which was stirred for 1 hour at 60° C. This mixture was cooled to room temperature, and partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (53.0 mg, 78%).

後処理

  1. customby irradiating ultrasonic wave for 1 minute
  2. concentrationThe reaction mixture was then concentrated under a reduced pressure
  3. customto obtain a white solid
  4. temperatureThis mixture was cooled to room temperature
  5. custompartitioned into water and ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with water and saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under a reduced pressure
  11. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

出典と根拠

ORDレコード
ord-7b9d464ebb0d4d87a8b1222d7741c1b8
出典データセット
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08158657B2

反応ノート

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