3-(2-fluorophenyl)-3-oxopropanenitrile

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(2-Fluorophenyl)-3-oxopropanenitrile (1.5 g, 9.2 mmol) and 2-(1,3-dioxolan-2-yl)-3-pyridinamine (1.68 g, 10.12 mmol) were dissolved in toluene (100 mL). To the mixture was added catalytic amount of p-TSA (300 mg) and the reaction flask equipped with Dean-Stark assembly was heated for 4 h at 120° C. After completion of reaction, the reaction mixture was treated with water and ethyl acetate. The organic layer was separated and the aqueous layer was back extracted with ethyl acetate. The organic layers were combined and dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a thick oily mass. The oily mass was then purified by silica gel column chromatography using 20% of ethyl acetate and hexane as eluent to give 2-(2-fluorophenyl)-1,5-naphthyridine-3-carbonitrile: 1H-NMR (CDCl3) δ: 7.2-7.0 (m, 3H), 7.8-7.4 (m, 3H), 8.4 (d, 1H), 9.1 (s, 1H). the reaction flask equipped with Dean-Stark After completion of reaction The organic layer was separated the aqueous layer was back extracted with ethyl acetate dried over anhydrous Na2SO4 concentrated under reduced pressure to give a thick oily mass The oily mass was then purified by silica gel column chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(2-Fluorophenyl)-3-oxopropanenitrile (1.5 g, 9.2 mmol) and 2-(1,3-dioxolan-2-yl)-3-pyridinamine (1.68 g, 10.12 mmol) were dissolved in toluene (100 mL). To the mixture was added catalytic amount of p-TSA (300 mg) and the reaction flask equipped with Dean-Stark assembly was heated for 4 h at 120° C. After completion of reaction, the reaction mixture was treated with water and ethyl acetate. The organic layer was separated and the aqueous layer was back extracted with ethyl acetate. The organic layers were combined and dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a thick oily mass. The oily mass was then purified by silica gel column chromatography using 20% of ethyl acetate and hexane as eluent to give 2-(2-fluorophenyl)-1,5-naphthyridine-3-carbonitrile: 1H-NMR (CDCl3) δ: 7.2-7.0 (m, 3H), 7.8-7.4 (m, 3H), 8.4 (d, 1H), 9.1 (s, 1H). the reaction flask equipped with Dean-Stark After completion of reaction The organic layer was separated the aqueous layer was back extracted with ethyl acetate dried over anhydrous Na2SO4 concentrated under reduced pressure to give a thick oily mass The oily mass was then purified by silica gel column chromatography

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

Procedure: To a flask charged with KOtBu (4 g, 36 mmol) and ether (100 mL, dry) was added dropwise a mixture of 2-fluorobenzonitrile (2.1 g, 17.5 mmol) and MeCN (0.738 g, 18 mmol) at 0° C. After addition the mixture was stirred at RT. for 2 days. Water was added and the reaction and extracted with ether (3×100 mL). The organic layers were combined, washed with brine and dried (Na2SO4). The solvent was evaporated under reduced pressure to afford a yellow oil, which was dissolved in CH2Cl2 and the solution was acidified with 3M HCl. After stirring the solution at RT for 2 hours, the solution was extracted with dichloromethane (3×200 mL). The organic layers were combined, washed with brine and dried (Na2SO4). After filtration, the filtrate was concentrated in vacuo to give 3-(2-fluoro-phenyl)-3-oxo-propionitrile (2 g, 70% yield) as a yellow solid. was added dropwise After addition the mixture the reaction extracted with ether (3×100 mL) washed with brine dried (Na2SO4) The solvent was evaporated under reduced pressure to afford a yellow oil, which After stirring the solution at RT for 2 hours the solution was extracted with dichloromethane (3×200 mL) washed with brine dried (Na2SO4) After filtration the filtrate was concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(2-Fluorophenyl)-3-oxopropanenitrile (1.5 g, 9.2 mmol) and 2-(1,3-dioxolan-2-yl)-3-pyridinamine (1.68 g, 10.12 mmol) were dissolved in toluene (100 mL). To the mixture was added catalytic amount of p-TSA (300 mg) and the reaction flask equipped with Dean-Stark assembly was heated for 4 h at 120° C. After completion of reaction, the reaction mixture was treated with water and ethyl acetate. The organic layer was separated and the aqueous layer was back extracted with ethyl acetate. The organic layers were combined and dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a thick oily mass. The oily mass was then purified by silica gel column chromatography using 20% of ethyl acetate and hexane as eluent to give 2-(2-fluorophenyl)-1,5-naphthyridine-3-carbonitrile: 1H-NMR (CDCl3) δ: 7.2-7.0 (m, 3H), 7.8-7.4 (m, 3H), 8.4 (d, 1H), 9.1 (s, 1H). the reaction flask equipped with Dean-Stark After completion of reaction The organic layer was separated the aqueous layer was back extracted with ethyl acetate dried over anhydrous Na2SO4 concentrated under reduced pressure to give a thick oily mass The oily mass was then purified by silica gel column chromatography