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

HRID 77960

Reaktionsgleichung

Reaktionsgleichung von HRID 77960
O1CCCC1.[OH-].[Na+].[NH2:8][C:9]1[C:14]([C:15]2[O:19][N:18]=[C:17]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=3)[CH:16]=2)=[CH:13][CH:12]=[CH:11][N:10]=1.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:35]Cl)=[N:33][CH:34]=1>CN(C)C=O>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:35][O:27][C:24]2[CH:25]=[CH:26][C:21]([CH2:20][C:17]3[CH:16]=[C:15]([C:14]4[C:9]([NH2:8])=[N:10][CH:11]=[CH:12][CH:13]=4)[O:19][N:18]=3)=[CH:22][CH:23]=2)=[N:33][CH:34]=1

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 145171515-Chloro-2-(chloromethyl)pyridineHCID 251143864-(5-(2-Amino-pyridin-3-yl)isoxazol-3-ylmethyl)phenol

Produkt 1

HCID 592553073-(3-(4-(5-Chloro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineAusbeute 95,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

Tetrahydrofuran (3 mL) and a 5 N aqueous sodium hydroxide solution (22.4 μL, 0.11 mmol) were added to 4-(5-(2-amino-pyridine-3-yl)-isoxazole-3-ylmethyl)-phenol (30 mg, 0.11 mmol) described in Manufacturing Example 5-1-1, which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction solution was then concentrated under a reduced pressure to obtain a white solid. An N,N-dimethylformamide (1 mL) solution of 5-chloro-2-chloromethyl-pyridine (20 mg, 0.12 mmol) described in Manufacturing Example 63-1-2 was added to a suspension of this solid and N,N-dimethylformamide (1 mL), and 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 saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (41.1 mg, 93%).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-a015d0d03a5b41a6a6ea44660899e318
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841327B2

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