Ammonium Chloride → 6-Chloropyridine-3-carboximidamide

HRID 492419Notes

Reaction equation

HRID 492419 reaction equation
[Cl-].[NH4+:2].[Al](C)(C)C.[Cl:7][C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][N:9]=1>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[Cl:7][C:8]1[CH:15]=[CH:14][C:11]([C:12]([NH2:2])=[NH:13])=[CH:10][N:9]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 16682925Trimethylaluminum

Product 1

HCID 208192366-Chloropyridine-3-carboximidamideYield 40.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

Suspend ammonium chloride (1.16 g, 21.6 mmol) in toluene (10 mL). Cool to 0° C. and slowly add 2.0 M Al(CH3)3 in toluene (10.8 mL, 21.6 mmol) (see Tetrahedron Lett. 1990, 31(14), 1969-1972). After the gas stops evolving, add a solution of 6-chloronicotinonitrile (1.00 g, 7.22 mmol) in toluene (52 mL). Heat to 80° C. overnight. Cool the reaction mixture, then slowly pour into slurry of silica gel (40 g) in CHCl3 (200 mL). Stir for 10 minutes before filtering. Filter and wash the silica plug with methanol (2× 100 mL). Concentrate the filtrate and purify by 10 g SCX column washing with methanol and then eluting with 2.0 M NH3 in methanol to give the title compound (0.458 g, 40.8%): MS ES+ 155.9 (M+H)+: HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=1.2 min, 97.2% purity.

Workup

  1. temperatureHeat to 80° C. overnight
  2. temperatureCool the reaction mixture
  3. filtrationbefore filtering
  4. filtrationFilter
  5. washwash the silica plug with methanol (2× 100 mL)
  6. concentrationConcentrate the filtrate
  7. custompurify by 10 g SCX column
  8. washwashing with methanol
  9. washeluting with 2.0 M NH3 in methanol

Sources & evidence

ORD record
ord-d5ca6c6e24584341b540a5680456da91
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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