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

HRID 77890Notes

Reaction equation

HRID 77890 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[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: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:31][CH:32]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 216980592-(Chloromethyl)-5-fluoropyridineHCID 251143864-(5-(2-Amino-pyridin-3-yl)isoxazol-3-ylmethyl)phenol

Product 1

HCID 441597193-(3-(4-(5-Fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Tetrahydrofuran (10 mL) and 5 N aqueous sodium hydroxide solution (448 μL, 2.24 mmol) were added to 4-(5-(2-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (600 mg, 2.24 mmol) described in Manufacturing Example 5-1-1, which was irradiated by ultrasonic wave for 1 minute. The reaction solution was then concentrated under a reduced pressure to obtain a white solid. 2-Chloromethyl-5-fluoro-pyridine (359 mg, 2.46 mol) described in Manufacturing Example 41-2 and N,N-dimethylformamide (10 mL) were added to the resulting white solid and stirred for 1 hour at 60° C. After being cooled to room temperature, the reaction solution was partitioned into water and ethyl acetate. The organic layer was separated and concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (650 mg, 77%).

Workup

  1. customwas irradiated by ultrasonic wave for 1 minute
  2. concentrationThe reaction solution was then concentrated under a reduced pressure
  3. customto obtain a white solid
  4. additionwere added to the resulting white solid
  5. temperatureAfter being cooled to room temperature
  6. customthe reaction solution was partitioned into water and ethyl acetate
  7. customThe organic layer was separated
  8. concentrationconcentrated under a reduced pressure
  9. customThe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-5ac2df75dae8479f9fe0eb0a8a1d4ef0
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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