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

HRID 1691067

Reaction equation

HRID 1691067 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: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

Participants

6

Reactant 4

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

Product 1

HCID 592553073-(3-(4-(5-Chloro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 95.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

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-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%).

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 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)

Sources & evidence

ORD record
ord-b013e70371304376a2cdcb73ac8a1522
Source dataset
uspto-grants-2012_04
Patent number
US08153662B2

Linked notes

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