3-(2-fluoroanilino)propanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2M Oxalyl chloride solution in dichloromethane (0.090 ml) and DMF (0.001 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.059 g) in anhydrous dichloromethane (1 ml). The reaction was stirred at room temperature for 1.5 h then a solution of 3-(2-fluoro-phenylamino)propionitrile (0.026 g) in dichloromethane (1 ml), DMAP (0.002 g) and DIPEA (0.078 m l) were added. The reaction mixture was stirred at room temperature for 66 h. The reaction mixture was partitioned between ethyl acetate and 1M aqueous hydrochloric acid. The aqueous layer was removed and the organic phase washed with further 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, water and dried with brine and over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with ethyl acetate:cyclohexane (4:1 v/v), to give the title compound as a colourless gum (0.028 g). The reaction mixture was stirred at room temperature for 66 h The reaction mixture was partitioned between ethyl acetate and 1M aqueous hydrochloric acid The aqueous layer was removed the organic phase washed with further 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, water dried with brine and over sodium sulphate concentrated under reduced pressure The residue was purified by flash column chromatography eluting with ethyl acetate:cyclohexane (4:1 v/v)

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

Procedure: 2M Oxalyl chloride solution in dichloromethane (0.090 ml) and DMF (0.001 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.059 g) in anhydrous dichloromethane (1 ml). The reaction was stirred at room temperature for 1.5 h then a solution of 3-(2-fluoro-phenylamino)propionitrile (0.026 g) in dichloromethane (1 ml), DMAP (0.002 g) and DIPEA (0.078 m l) were added. The reaction mixture was stirred at room temperature for 66 h. The reaction mixture was partitioned between ethyl acetate and 1M aqueous hydrochloric acid. The aqueous layer was removed and the organic phase washed with further 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, water and dried with brine and over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with ethyl acetate:cyclohexane (4:1 v/v), to give the title compound as a colourless gum (0.028 g). The reaction mixture was stirred at room temperature for 66 h The reaction mixture was partitioned between ethyl acetate and 1M aqueous hydrochloric acid The aqueous layer was removed the organic phase washed with further 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, water dried with brine and over sodium sulphate concentrated under reduced pressure The residue was purified by flash column chromatography eluting with ethyl acetate:cyclohexane (4:1 v/v)