Water → 5-((6-Chloropyrimidin-4-yl)oxy)pyridin-2-amine

HRID 1049317Notes

Reaction equation

HRID 1049317 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:17]=[C:16](Cl)[N:15]=[CH:14][N:13]=1.O>CC(N(C)C)=O>[Cl:11][C:12]1[N:13]=[CH:14][N:15]=[C:16]([O:10][C:7]2[CH:6]=[CH:5][C:4]([NH2:3])=[N:9][CH:8]=2)[CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 709434,6-DichloropyrimidineHCID 42319722-Amino-5-hydroxypyridine

Product 1

HCID 904032395-((6-Chloropyrimidin-4-yl)oxy)pyridin-2-amineYield 49.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

A −10° C. suspension of NaH (60% in mineral oil, 0.726 g, 18.16 mmol) in anhydrous DMA (15 mL) was treated with 6-aminopyridin-3-ol (1.0 g, 9.08 mmol), stirred cold for 30 min, treated drop-wise with a solution of 4,6-dichloropyrimidine (2.029 g, 13.62 mmol) in DMA (10 mL), warmed to RT and stirred for 2 h. The mixture was treated with H2O, extracted with DCM (3×) and the combined organics were washed with 5% LiCl, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc) to afford 5-((6-chloropyrimidin-4-yl)oxy)pyridin-2-amine (1.0 g, 49%). 1H NMR (400 MHz, DMSO-d6): δ 8.62 (d, J=0.9 Hz, 1H), 7.79 (d, J=2.9 Hz, 1H), 7.33-7.26 (m, 2H), 6.48 (d, J=8.9 Hz, 1H), 6.00 (s, 2H); MS (ESI) m/z: 223.0 (M+H+).

Workup

  1. stirringstirred for 2 h
  2. extractionextracted with DCM (3×)
  3. washthe combined organics were washed with 5% LiCl
  4. dry with materialbrine, dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified via silica gel chromatography (EtOAc)

Sources & evidence

ORD record
ord-3959a9d2d3be48a4b7e7044ec6171016
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…