4-Chloro-N-methylpicolinamide → HCID 90410540, compound

HRID 626515Notes

Reaction equation

HRID 626515 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.CC(C)([O-])C.[K+].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]([NH:24][CH3:25])=[O:23])[CH:17]=1>CC(N(C)C)=O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([O:8][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([C:22]([NH:24][CH3:25])=[O:23])[CH:17]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14768144-Chloro-N-methylpicolinamideHCID 42319722-Amino-5-hydroxypyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 90410540HCID 90410540, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 2-amino-5-hydroxypyridine (0.968 g, 8.79 mmol) in DMA (15 mL) was treated with potassium tert-butoxide (0.987 g, 8.79 mmol), stirred at RT for 3 h, treated with 4-chloro-N-methylpicolinamide (1.5 g, 8.79 mmol) and stirred at RT for 2 days. The mixture was concentrated to dryness, treated with water, extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc, MeOH/DCM) to afford 4-((6-aminopyridin-3-yl)oxy)-N-methylpicolinamide (1.3 g, 61%). 1H NMR (400 MHz, DMSO-d6): δ 8.75 (m, 1H), 8.46 (d, J=5.6 Hz, 1H), 7.82 (d, J=2.9 Hz, 1H), 7.34 (d, J=2.6 Hz, 1H), 7.30 (dd, J=8.9, 3.0 Hz, 1H), 7.10 (dd, J=5.6, 2.7 Hz, 1H), 6.53 (d, J=8.9 Hz, 1H), 6.07 (s, 2H), 2.77 (d, J=4.8 Hz, 3H); MS (ESI) m/z: 245.1 (M+H+).

Workup

  1. stirringstirred at RT for 2 days
  2. concentrationThe mixture was concentrated to dryness
  3. additiontreated with water
  4. extractionextracted with EtOAc (3×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (EtOAc, MeOH/DCM)

Sources & evidence

ORD record
ord-9cdca85dc2a14f1c93b504dcedce0741
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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