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

HRID 78101Notes

Reaction equation

HRID 78101 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17](Cl)=[N:18][OH:19])=[CH:12][CH:11]=2)[CH:3]=1.[C:21]([C:23]1[C:24]([NH2:30])=[N:25][C:26]([NH2:29])=[CH:27][CH:28]=1)#[CH:22].C(N(CC)CC)C>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]3[CH:22]=[C:21]([C:23]4[C:24]([NH2:30])=[N:25][C:26]([NH2:29])=[CH:27][CH:28]=4)[O:19][N:18]=3)=[CH:12][CH:11]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 72262858(4-(4-Fluoro-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride

Product 1

HCID 592552753-(3-(4-(4-Fluoropyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 66.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a tetrahydrofuran (3 mL) solution of (4-(4-fluoro-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride (200 mg, 0.679 mmol) described in Manufacturing Example 59-1-5 and 3-ethynyl-pyridin-2,6-diamine (57.7 mg, 0.433 mmol) described in Manufacturing Example 13-1-3 was added triethylamine (237 μL, 1.7 mmol). This mixture was stirred for 4 hours at room temperature. This mixture was 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˜ethyl acetate) to obtain the title compound (113 mg, 43%).

Workup

  1. customThis mixture was partitioned into water and ethyl acetate
  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 (heptane: ethyl acetate=1:1˜ethyl acetate)

Sources & evidence

ORD record
ord-198e1cda89be47288c4d99898f1778cb
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

Loading…