Triethylamine → 3-(3-(4-Phenoxymethyl-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 78145Notes

Reaction equation

HRID 78145 reaction equation
[O:1]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](Cl)=[N:17][OH:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([C:22]1[C:23]([NH2:29])=[N:24][C:25]([NH2:28])=[CH:26][CH:27]=1)#[CH:21].C(N(CC)CC)C>O1CCCC1>[O:1]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[CH:21]=[C:20]([C:22]3[C:23]([NH2:29])=[N:24][C:25]([NH2:28])=[CH:26][CH:27]=3)[O:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 72262854(4-Phenoxymethyl-phenyl)-acetohydroximoyl chloride

Product 1

HCID 592551073-(3-(4-Phenoxymethyl-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 34.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a tetrahydrofuran (3 mL) solution of (4-phenoxymethyl-phenyl)-acetohydroximoyl chloride (150 mg, 0.545 mmol) described in Manufacturing Example 86-1-5 and 3-ethynyl-pyridin-2,6-diamine (46.3 mg, 0.348 mmol) described in Manufacturing Example 13-1-3 was added triethylamine (104 μL, 0.747 mmol), which was stirred for 1 hour at room temperature. This mixture was 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 was purified by NH silica gel column chromatography (ethyl acetate) to obtain the title compound (45 mg, 22%).

Workup

  1. customThis mixture was partitioned into ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-a94986d842224cfdb55e45e4d98e3b50
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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