3-chloro-4-oxopentanenitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-5-benzylamino pyridine (4.0 g), triethylamine (2.1 g),3-chloro-4-oxopentanenitrile (2.7 g) and acetonitrile (50 ml) is stirred and heated under reflux for 18 hr. The solvent is removed in vacuo, and the residue is dissolved in chloroform (200 ml). The solution is washed with water (4×100 ml), dried over anhydrous potassium carbonate and the chloroform is removed in vacuo. The residue is chromatographed on silica gel (200 g) using chloroform as the eluant. The product is obtainedand crystallized from acetonitrile. heated under reflux for 18 hr The solvent is removed in vacuo the residue is dissolved in chloroform (200 ml) The solution is washed with water (4×100 ml) dried over anhydrous potassium carbonate the chloroform is removed in vacuo The residue is chromatographed on silica gel (200 g) The product is obtainedand crystallized from acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In similar manner, reaction of 2-amino-3-(2-phenylethyl)pyridine (which is prepared by amination of 3-(2-phenyl ethyl)-pyridine with sodium amide in ammonia and N,N-dimethylaniline) with 3-chloro-4-oxo-pentanonitrile in ethanol in the presence of triethylamine gives 3-cyano-methyl-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In similar manner, reaction of 2-amino-3-(2-phenylethyl)pyridine (which is prepared by amination of 3-(2-phenyl ethyl)-pyridine with sodium amide in ammonia and N,N-dimethylaniline) with 3-chloro-4-oxo-pentanonitrile in ethanol in the presence of triethylamine gives 3-cyano-methyl-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.3 g of 2-amino-3-(3-phenylpropoxy)pyridine, 3.2 g of 3-chloro-4-oxopentanonitrile, 2.0 g sodium bicarbonate, and 50 ml dimethoxyethane was heated at reflux for 24 hrs., then stirred at room temperature 66 hrs. the solvent was removed in vacuo, the brown residue was taken up in 100 ml methylene chloride, filtered, dried over potassium carbonate and evaporated in vacuo to leave a brown gum residue. The residue was chromatographed on silica gel using first chloroform, then switching to 1:1 chloroform/ethyl acetate. The early eluates were combinedand evaporated and the resultant residue crystallized from isopropyl/ether to give the title compound (m.p. 143°-145° C.). was heated at reflux for 24 hrs the solvent was removed in vacuo filtered dried over potassium carbonate evaporated in vacuo to leave a brown gum residue The residue was chromatographed on silica gel using first chloroform The early eluates were combinedand evaporated the resultant residue crystallized from isopropyl/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 0.86 g. of 3-chloro-4-oxopentanonitrile, 0.92 g. of 2-amino-3-phenylmethoxypyridine and 0.5 ml. of triethylamine in 15 ml. of ethanol was stirred for 16 hours, then concentrated to remove the triethylamine and ethanol. The residue was dissolved in methylene chlorideand washed with water. The methylene chloride was concentrated and the residual oil was dissolved in 20 ml. of boiling acetonitrile, filtered, cooled, and treated with hydrogen chloride/methanol with cooling to give 0.22 g. of the desired product (m.p. 163°-166° C.). concentrated to remove the triethylamine and ethanol The residue was dissolved in methylene chlorideand washed with water The methylene chloride was concentrated the residual oil was dissolved in 20 ml of boiling acetonitrile, filtered cooled treated with hydrogen chloride/methanol with cooling to give 0.22 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-5-benzylamino pyridine (4.0 g), triethylamine (2.1 g),3-chloro-4-oxopentanenitrile (2.7 g) and acetonitrile (50 ml) is stirred and heated under reflux for 18 hr. The solvent is removed in vacuo, and the residue is dissolved in chloroform (200 ml). The solution is washed with water (4×100 ml), dried over anhydrous potassium carbonate and the chloroform is removed in vacuo. The residue is chromatographed on silica gel (200 g) using chloroform as the eluant. The product is obtainedand crystallized from acetonitrile. heated under reflux for 18 hr The solvent is removed in vacuo the residue is dissolved in chloroform (200 ml) The solution is washed with water (4×100 ml) dried over anhydrous potassium carbonate the chloroform is removed in vacuo The residue is chromatographed on silica gel (200 g) The product is obtainedand crystallized from acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In similar manner, reaction of 2-amino-3-(2-phenylethyl)pyridine (which is prepared by amination of 3-(2-phenyl ethyl)-pyridine with sodium amide in ammonia and N,N-dimethylaniline) with 3-chloro-4-oxo-pentanonitrile in ethanol in the presence of triethylamine gives 3-cyano-methyl-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.3 g of 2-amino-3-(3-phenylpropoxy)pyridine, 3.2 g of 3-chloro-4-oxopentanonitrile, 2.0 g sodium bicarbonate, and 50 ml dimethoxyethane was heated at reflux for 24 hrs., then stirred at room temperature 66 hrs. the solvent was removed in vacuo, the brown residue was taken up in 100 ml methylene chloride, filtered, dried over potassium carbonate and evaporated in vacuo to leave a brown gum residue. The residue was chromatographed on silica gel using first chloroform, then switching to 1:1 chloroform/ethyl acetate. The early eluates were combinedand evaporated and the resultant residue crystallized from isopropyl/ether to give the title compound (m.p. 143°-145° C.). was heated at reflux for 24 hrs the solvent was removed in vacuo filtered dried over potassium carbonate evaporated in vacuo to leave a brown gum residue The residue was chromatographed on silica gel using first chloroform The early eluates were combinedand evaporated the resultant residue crystallized from isopropyl/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 0.86 g. of 3-chloro-4-oxopentanonitrile, 0.92 g. of 2-amino-3-phenylmethoxypyridine and 0.5 ml. of triethylamine in 15 ml. of ethanol was stirred for 16 hours, then concentrated to remove the triethylamine and ethanol. The residue was dissolved in methylene chlorideand washed with water. The methylene chloride was concentrated and the residual oil was dissolved in 20 ml. of boiling acetonitrile, filtered, cooled, and treated with hydrogen chloride/methanol with cooling to give 0.22 g. of the desired product (m.p. 163°-166° C.). concentrated to remove the triethylamine and ethanol The residue was dissolved in methylene chlorideand washed with water The methylene chloride was concentrated the residual oil was dissolved in 20 ml of boiling acetonitrile, filtered cooled treated with hydrogen chloride/methanol with cooling to give 0.22 g