2-Aminopyridine → 3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde

HRID 1503548Notes

Reaction equation

HRID 1503548 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[Cl:11].C([O-])([O-])=O.[K+].[K+].[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>CN(C)C(=O)C.O>[Cl:11][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:3]=1[CH2:2][NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH:7]=[O:8]

Participants

6

Reactant 3

HCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 866751774-(Bromomethyl)-3-chlorobenzaldehyde

Product 1

HCID 866751823-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehydeYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in N,N-dimethylacetamide (DMA; 20 mL) was added K2CO3 (2.36 g, 17.16 mmol) and 2-aminopyridine (0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with H2O and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO2, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as off-white solid (1.05 g, 50%): mp 122-123° C.; 1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H), 7.4 (m, 1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s, 1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]+).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography (SiO2, 100-200 mesh; 20% EtOAc in n-Hexane)

Sources & evidence

ORD record
ord-60a67c04fcd04a57bb19febd21d19c3b
Source dataset
uspto-grants-2015_12
Patent number
US09212163B2

Reaction notes

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