Tetrahydrofuran → 3-(3-(4-(6-Chloro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 1891639Notes

Reaction equation

HRID 1891639 reaction equation
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:34]=[CH:33][CH:32]=[C:31]([CH2:35]Cl)[N:30]=1>CN(C)C=O>[Cl:28][C:29]1[N:30]=[C:31]([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)[CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 155744402-Chloro-6-(chloromethyl)pyridineHCID 251143864-(5-(2-Amino-pyridin-3-yl)isoxazol-3-ylmethyl)phenol

Product 1

HCID 441597223-(3-(4-(6-Chloro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 91.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Tetrahydrofuran (3 mL) and a 5 N aqueous sodium hydroxide solution (22.4 μL, 0.11 mmol) were added to 4-(5-(2-amino-pyridin-3-yl)isoxazol-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-dimethylfornamide (1 mL) solution of 2-chloro-6-chloromethyl-pyridine (36.3 mg, 0.22 mmol) described in Manufacturing Example 52-1-2 was added to a suspension of this solid and N,N-dimethylformamide (1 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 (39.5 mg, 90%).

Workup

  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 water and 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 residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-0d52ed29a5c94141822bca515645eda4
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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