Triethylamine → 3-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-5-fluoro-pyridin-2-ylamine

HRID 78180Notes

Reaction equation

HRID 78180 reaction equation
[C:1]([C:3]1[C:4]([NH2:10])=[N:5][CH:6]=[C:7]([F:9])[CH:8]=1)#[CH:2].[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26](Cl)=[N:27][OH:28])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>O1CCCC1>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]2[CH:2]=[C:1]([C:3]3[C:4]([NH2:10])=[N:5][CH:6]=[C:7]([F:9])[CH:8]=3)[O:28][N:27]=2)=[CH:21][CH:20]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 552886203-Ethynyl-5-fluoropyridin-2-amineHCID 722628734-Benzyloxy-phenyl-acetohydroximoyl chloride

Product 1

HCID 592554543-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-5-fluoro-pyridin-2-ylamineYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a tetrahydrofuran (10 mL) mixture of 3-ethynyl-5-fluoro-pyridin-2-ylamine (129 mg, 0.95 mmol) described in Manufacturing Example 173-1-2 and 4-benzyloxy-phenyl-acetohydroximoyl chloride (314 mg, 1.14 mmol) described in Manufacturing Example 1-1-3 was added triethylamine (264 μL, 1.90 mmol) at room temperature, which was stirred for 1 hour at 55° C., and then for another hour at 60° C. This reaction mixture was cooled to room temperature, and then partitioned into ethyl acetate and water. 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 thus obtained was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (212 mg, 60%).

Workup

  1. waitfor another hour at 60° C
  2. temperatureThis reaction mixture was cooled to room temperature
  3. custompartitioned into ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under a reduced pressure
  9. customthe residue thus obtained
  10. customwas purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-cfe1854f64a94e8a8b142052fd33b2ea
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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