3-(bromomethyl)-5-chlorobenzonitrile

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

Procedure: The title compound was prepared following general procedure 10, starting from 3-(bromomethyl)-5-chlorobenzonitrile and sarcosine tert-butyl ester hydrochloride. It was isolated as a yellow oil (570 mg, 78%). LC/MS (Method B): 295.1 (M+H)+.

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

Procedure: The title compound was prepared following general procedure 10, starting from 3-(bromomethyl)-5-chlorobenzonitrile and sarcosine tert-butyl ester hydrochloride. It was isolated as a yellow oil (570 mg, 78%). LC/MS (Method B): 295.1 (M+H)+.

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

Procedure: The title compound was prepared following general procedure 10, starting from 3-(bromomethyl)-5-chlorobenzonitrile and sarcosine tert-butyl ester hydrochloride. It was isolated as a yellow oil (570 mg, 78%). LC/MS (Method B): 295.1 (M+H)+.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Step 4) To a solution of 2-amino-5-chloronicotinamide (0.15 g) in N,N-dimethylformamide (3 ml) was added 3-(bromomethyl)-5-chlorobenzonitrile (0.29 g) obtained in Step 3, and the mixture was stirred at 100° C. for 14 hr. The reaction mixture was diluted with ethyl acetate. The precipitate was collected by filtration and washed with ethyl acetate. The obtained precipitate was recrystallized from methanol-ethyl acetate to give the title compound (80 mg). The precipitate was collected by filtration washed with ethyl acetate The obtained precipitate was recrystallized from methanol-ethyl acetate

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

Procedure: (Step 3) Triphenylphosphine (0.94 g) was suspended in acetonitrile (20 ml), bromine (0.19 ml) was added, and the mixture was stirred for 30 min. A solution (10 ml) of 3-chloro-5-(hydroxymethyl)benzonitrile (0.60 g) obtained in Step 2 in acetonitrile was added to the reaction mixture, and the mixture was stirred at 80° C. for 4 hr. The reaction solution was quenched with water, and the mixture was extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogen carbonate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was treated by basic silica gel chromatography (ethyl acetate:hexane=1:2) to give 3-(bromomethyl)-5-chlorobenzonitrile (0.31 g) as a white solid. the mixture was stirred at 80° C. for 4 hr The reaction solution was quenched with water the mixture was extracted with ethyl acetate The extract was washed with aqueous sodium hydrogen carbonate solution with saturated brine, and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the obtained residue was treated by basic silica gel chromatography (ethyl acetate:hexane=1:2)