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

HRID 640474Notes

Reaction equation

HRID 640474 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([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:4][CH:3]=1.O1CCCC1.[OH-].[Na+].Cl[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=1>CN(C)C=O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][O:20][C:17]2[CH:18]=[CH:19][C:14]([CH2:13][C:10]3[CH:9]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([NH2:1])=[N:7][CH:6]=4)[O:12][N:11]=3)=[CH:15][CH:16]=2)=[N:31][CH:32]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 216980592-(Chloromethyl)-5-fluoropyridineHCID 592554134-(5-(6-Amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol

Product 1

HCID 592551795-(3-(4-(5-Fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 11.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To 4-(5-(6-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (20.0 mg, 0.07 mmol) described in Manufacturing Example 177-1-1 were added tetrahydrofuran (3 mL) and a 5 N sodium hydroxide aqueous solution (14.9 μL, 0.07 mmol), which was dissolved by irraditaing ultrasonic wave for 1 minute. The reaction solution was concentrated under a reduced pressure, which gave a white solid. To a mixture of the solid obtained above and N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of the 2-chloromethyl-5-fluoro-pyridine (12.0 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 (3.0 mg, 11%).

Workup

  1. concentrationThe reaction solution was concentrated under a reduced pressure, which
  2. customgave a white solid
  3. additionTo a mixture of the 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)

Sources & evidence

ORD record
ord-13bd57d2089e408c8ee608ab7b7adb89
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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