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

HRID 78183노트

반응식

HRID 78183 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
60 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-95dc369378d54fd8af6ef70e4e6e22a2
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841327B2

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