5-fluoro-2-piperazin-1-ylbenzonitrile

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of piperazine (Aldrich; 1.28 g), 2,5-difluorobenzonitrile (Lancaster; 0.422 g), and DMF (4mL) is stirred at 80° C. for 1.5 h, after which the mixture is cooled and partitioned between dichloromethane, water, and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate, concentrated, and the residue is crystallized from dichloromethane/ethyl ether/hexane to give 0.282 g of 5-fluoro-2-(piperazin-1-yl)benzonitrile; mp 83-83.5° C.; 1H NMR (CDCl3) δ 3.10, 7.00, 7.21, 7.21, 7.27. after which the mixture is cooled partitioned between dichloromethane, water, and aq. sodium bicarbonate The organic layers are dried over sodium sulfate concentrated the residue is crystallized from dichloromethane/ethyl ether/hexane

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

Procedure: Following the general procedure of Example 11 and making noncritical variations, 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (Example 4, Step 1; 0.199 g), 5-fluoro-2-(piperazin-1-yl)benzonitrile (0.203 g), triethylamine (0.110 g), and ethylene glycol (2 mL) give 0.218 g of the title compound after chromatography (silica gel, methanol/dichloromethane, 4/96) and crystallization from dichloromethane/hexane; mp 179-180° C.; MS m/z 369; IR (mineral oil) 1494, 1329, 808, 1452, 1072 cm-1. 1H NMR (CDCl3) δ2.78, 3.20, 3.78, 6.99, 7.13, 7.19, 7.26, 7.51, 7.52.8.14.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of piperazine (Aldrich; 1.28 g), 2,5-difluorobenzonitrile (Lancaster; 0.422 g), and DMF (4 mL) is stirred at 80° C. for 1.5 h, after which the mixture is cooled and partitioned between dichloromethane, water, and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate, concentrated, and the residue is crystallized from dichloromethane/ethyl ether/hexane to give 0.282 g of 5-fluoro-2-(piperazin-1-yl)benzonitrile; mp 83-83.5° C.; 1H NMR (CDCl3) δ3.10, 7.00, 7.21, 7.27. after which the mixture is cooled partitioned between dichloromethane, water, and aq. sodium bicarbonate The organic layers are dried over sodium sulfate concentrated the residue is crystallized from dichloromethane/ethyl ether/hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of piperazine (Aldrich; 1.28 g), 2,5-difluorobenzonitrile (Lancaster; 0.422 g), and DMF (4mL) is stirred at 80° C. for 1.5 h, after which the mixture is cooled and partitioned between dichloromethane, water, and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate, concentrated, and the residue is crystallized from dichloromethane/ethyl ether/hexane to give 0.282 g of 5-fluoro-2-(piperazin-1-yl)benzonitrile; mp 83-83.5° C.; 1H NMR (CDCl3) δ 3.10, 7.00, 7.21, 7.21, 7.27. after which the mixture is cooled partitioned between dichloromethane, water, and aq. sodium bicarbonate The organic layers are dried over sodium sulfate concentrated the residue is crystallized from dichloromethane/ethyl ether/hexane