3-(3-fluorophenyl)-3-oxopropanenitrile

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-(3-fluorophenyl)-3-oxopropanenitrile (0.8991 g, 5.511 mmol) and 3-amino-2-pyridinecarbaldehyde (0.6730 g, 5.511 mmol) in ethyl acetate (16.70 mL, 5.511 mmol) was added piperidine (0.04360 mL, 0.4409 mmol) and the mixture was heated under reflux (bath temp. 85° C.) with stirring. After 1 h, the mixture was cooled to room temperature and concentrated under reduced pressure to give a dark brown solid. The dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 2-(3-fluorophenyl)-1,5-naphthyridine-3-carbonitrile as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.27 (1H, d, J=0.8 Hz), 9.18 (1H, dd, J=4.1, 1.8 Hz), 8.56-8.62 (1H, m), 8.01 (1H, dd, J=8.6, 3.9 Hz), 7.76-7.85 (2H, m), 7.63-7.71 (1H, m), 7.44-7.52 (1H, m); LC-MS (ESI) m/z 249.9 [M+H]+. the mixture was heated the mixture was cooled to room temperature concentrated under reduced pressure to give a dark brown solid The dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column over 25 min

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

Procedure: 5 g (34.0 mmol) of 3-oxo-3-(3-fluorophenyl)-propanenitrile were dissolved in pyridine (30 ml) and thiourea (5 g, 68.0 mmol) and iodine (8.70 g, 34.40 mmol) were added successively. The solution was stirred at 100° C. for 12 h. The mixture was then cooled to room temperature and poured into ice-water (500 ml). The resulting solid was filtered, washed with water and recrystallized from ethanol to give 7.0 g (91%) of a yellow solid. The mixture was then cooled to room temperature The resulting solid was filtered washed with water recrystallized from ethanol

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

Procedure: Example 72 (Compound 79) was synthesised following a similar procedure outlined in Example 68 (Compound 75), using 3-fluorobenzoylacetonitrile instead of 4-fluorobenzoylacetonitrile in step 1 and pyrrolidine instead of morpholine in step 7. Compound 79 was obtained as a yellow solid (13.1 mg). Example 72 (Compound 79) was synthesised

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

Procedure: Example 69 (Compound 76) was synthesised following a similar procedure outlined in Example 68 (Compound 75), using 3-fluorobenzoylacetonitrile instead of 4-fluorobenzoylacetonitrile in step 1. Compound 76 was obtained as a yellow solid (4.8 mg). Example 69 (Compound 76) was synthesised

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

Procedure: Example 72 (Compound 79) was synthesised following a similar procedure outlined in Example 68 (Compound 75), using 3-fluorobenzoylacetonitrile instead of 4-fluorobenzoylacetonitrile in step 1 and pyrrolidine instead of morpholine in step 7. Compound 79 was obtained as a yellow solid (13.1 mg). Example 72 (Compound 79) was synthesised

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

Procedure: Example 69 (Compound 76) was synthesised following a similar procedure outlined in Example 68 (Compound 75), using 3-fluorobenzoylacetonitrile instead of 4-fluorobenzoylacetonitrile in step 1. Compound 76 was obtained as a yellow solid (4.8 mg). Example 69 (Compound 76) was synthesised

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-(3-fluorophenyl)-3-oxopropanenitrile (0.8991 g, 5.511 mmol) and 3-amino-2-pyridinecarbaldehyde (0.6730 g, 5.511 mmol) in ethyl acetate (16.70 mL, 5.511 mmol) was added piperidine (0.04360 mL, 0.4409 mmol) and the mixture was heated under reflux (bath temp. 85° C.) with stirring. After 1 h, the mixture was cooled to room temperature and concentrated under reduced pressure to give a dark brown solid. The dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 2-(3-fluorophenyl)-1,5-naphthyridine-3-carbonitrile as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.27 (1H, d, J=0.8 Hz), 9.18 (1H, dd, J=4.1, 1.8 Hz), 8.56-8.62 (1H, m), 8.01 (1H, dd, J=8.6, 3.9 Hz), 7.76-7.85 (2H, m), 7.63-7.71 (1H, m), 7.44-7.52 (1H, m); LC-MS (ESI) m/z 249.9 [M+H]+. the mixture was heated the mixture was cooled to room temperature concentrated under reduced pressure to give a dark brown solid The dark brown solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column over 25 min