Ammonium Chloride → 6-Chloropyridine-3-carboximidamide

HRID 130810Notes

Reaction equation

HRID 130810 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). Beat 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. customto 80° C.
  2. customovernight
  3. temperatureCool the reaction mixture
  4. filtrationbefore filtering
  5. filtrationFilter
  6. washwash the silica plug with methanol (2×100 mL)
  7. concentrationConcentrate the filtrate
  8. custompurify by 10 g SCX column
  9. washwashing with methanol
  10. washeluting with 2.0 M NH3 in methanol

Sources & evidence

ORD record
ord-1036ac709a64447a80d70b72c975f170
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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