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

HRID 1691289ノート

反応式

HRID 1691289 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][C:5]([F:21])=[CH:4][N:3]=1.O1CCCC1.[OH-].[Na+].Cl[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][N:32]=1>CN(C)C=O>[F:21][C:5]1[CH:6]=[C:7]([C:8]2[O:12][N:11]=[C:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][N:32]=4)=[CH:16][CH:15]=3)[CH:9]=2)[C:2]([NH2:1])=[N:3][CH:4]=1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 216980592-(Chloromethyl)-5-fluoropyridineHCID 592555204-(5-(2-Amino-5-fluoro-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol

生成物 1

HCID 592553035-Fluoro-3-(3-(4-(5-fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)pyridin-2-ylamine収率 89.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
60 °C

実験手順

To 4-(5-(2-amino-5-fluoro-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (20.0 mg, 0.07 mmol) described in Manufacturing Example 174-1-1 were added tetrahydrofuran (3 mL) and a 5 N sodium hydroxide aqueous solution (14.0 μL, 0.07 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. Next, the reaction solution was concentrated under a reduced pressure, which gave a white solid. To a mixture of this solid and N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-5-fluoro-pyridine (11.2 mg, 0.08 mmol) described in manufacturing Example 41-1-2, which was stirred for 1 hour at 60° C. The reaction mixture was cooled to room temperature and then 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 (24.7 mg, 89%).

後処理

  1. customby irradiating ultrasonic wave for 1 minute
  2. concentrationNext, the reaction solution was concentrated under a reduced pressure, which
  3. customgave a white solid
  4. temperatureThe reaction 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-824742be4f784d85aa175dace87edf38
出典データセット
uspto-grants-2012_04
特許番号
US08153662B2

反応ノート

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