methyl 3-(2-methylsulfonylphenyl)-3-oxopropanoate

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

Procedure: A mixture of 3-aminopicolinaldehyde (1.09 g, 8.97 mmol), methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate (2.3 g, 8.97 mmol) and cerium chloride heptahydrate (587 mg, 1.79 mmol) was heated to 100° C. for 3 h. The residue was dissolved in MeOH and purified by column chromatography on neutral alumina using 0-50% EtOAc in hexane to give methyl 2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridine-3-carboxylate (800 mg, 26% yield): 1H NMR (400 MHz, DMSO-d6) δ 3.155 (s, 3H), 3.688 (s, 3H), 7.486-7.507 (m, 1H), 7.733-7.816 (m, 2H), 7.951-7.982 (m, 1H), 8.059-8.081 (m, 1H), 8.510 (d, J=8.4 Hz, 1H), 8.965 (s, 1H), 9.165-9.178 (m, 1H); LC-MS (ESI) m/z 342.9 [M+H]+. purified by column chromatography on neutral alumina using 0-50% EtOAc in hexane

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

Procedure: A mixture of 3-amino-5-fluoropicolinaldehyde (930 mg, 6.63 mmol), methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate (1.7 g, 6.63 mmol) and cerium chloride heptahydrate (435 mg, 1.32 mmol) was heated to 100° C. for 3 h. The residue was dissolved in MeOH and purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane to give methyl 7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridine-3-carboxylate: LC-MS (ESI) m/z 361.0 [M+H]+. purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane

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

Procedure: A mixture of 3-amino-5-fluoropicolinaldehyde (930 mg, 6.63 mmol), methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate (1.7 g, 6.63 mmol) and cerium chloride heptahydrate (435 mg, 1.32 mmol) was heated to 100° C. for 3 h. The residue was dissolved in MeOH and purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane to give methyl 7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridine-3-carboxylate: LC-MS (ESI) m/z 361.0 [M+H]+. purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(2-(methylsulfonyl)phenyl)-3-oxopropanenitrile (4.5 g, 20.25 mmol) in methanol (100 mL) was added trimethyl silyl chloride (11 mL, 100.58 mmol) at 25° C. The reaction mixture was stirred for overnight at 70° C. Water was added to the reaction mixture at 25° C. and extracted with EtOAc. The reaction mixture was concentrated in vacuo and purified by column chromatography on silica gel using 0-30% EtOAc in hexane to give methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate: 1H NMR (400 MHz, DMSO-d6): δ 3.294 (S, 3H), 3.645 (s, 3H), 4.12 (s, 2H), 7.762-7.874 (m, 3H), 7.979-7.984 (m, 1H); LC-MS (ESI) m/z 256.9 [M+H]+. extracted with EtOAc The reaction mixture was concentrated in vacuo purified by column chromatography on silica gel using 0-30% EtOAc in hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(2-(methylsulfonyl)phenyl)-3-oxopropanenitrile (4.5 g, 20.25 mmol) in methanol (100 mL) was added trimethyl silyl chloride (11 mL, 100.58 mmol) at 25° C. The reaction mixture was stirred for overnight at 70° C. Water was added to the reaction mixture at 25° C. and extracted with EtOAc. The reaction mixture was concentrated in vacuo and purified by column chromatography on silica gel using 0-30% EtOAc in hexane to give methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate: 1H NMR (400 MHz, DMSO-d6): δ 3.294 (S, 3H), 3.645 (s, 3H), 4.12 (s, 2H), 7.762-7.874 (m, 3H), 7.979-7.984 (m, 1H); LC-MS (ESI) m/z 256.9 [M+H]+. extracted with EtOAc The reaction mixture was concentrated in vacuo purified by column chromatography on silica gel using 0-30% EtOAc in hexane

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

Procedure: A mixture of 3-aminopicolinaldehyde (1.09 g, 8.97 mmol), methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate (2.3 g, 8.97 mmol) and cerium chloride heptahydrate (587 mg, 1.79 mmol) was heated to 100° C. for 3 h. The residue was dissolved in MeOH and purified by column chromatography on neutral alumina using 0-50% EtOAc in hexane to give methyl 2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridine-3-carboxylate (800 mg, 26% yield): 1H NMR (400 MHz, DMSO-d6) δ 3.155 (s, 3H), 3.688 (s, 3H), 7.486-7.507 (m, 1H), 7.733-7.816 (m, 2H), 7.951-7.982 (m, 1H), 8.059-8.081 (m, 1H), 8.510 (d, J=8.4 Hz, 1H), 8.965 (s, 1H), 9.165-9.178 (m, 1H); LC-MS (ESI) m/z 342.9 [M+H]+. purified by column chromatography on neutral alumina using 0-50% EtOAc in hexane

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

Procedure: A mixture of 3-amino-5-fluoropicolinaldehyde (930 mg, 6.63 mmol), methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate (1.7 g, 6.63 mmol) and cerium chloride heptahydrate (435 mg, 1.32 mmol) was heated to 100° C. for 3 h. The residue was dissolved in MeOH and purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane to give methyl 7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridine-3-carboxylate: LC-MS (ESI) m/z 361.0 [M+H]+. purified by column chromatography on neutral alumina using 0-30% EtOAc in hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(2-(methylsulfonyl)phenyl)-3-oxopropanenitrile (4.5 g, 20.25 mmol) in methanol (100 mL) was added trimethyl silyl chloride (11 mL, 100.58 mmol) at 25° C. The reaction mixture was stirred for overnight at 70° C. Water was added to the reaction mixture at 25° C. and extracted with EtOAc. The reaction mixture was concentrated in vacuo and purified by column chromatography on silica gel using 0-30% EtOAc in hexane to give methyl 3-(2-(methylsulfonyl)phenyl)-3-oxopropanoate: 1H NMR (400 MHz, DMSO-d6): δ 3.294 (S, 3H), 3.645 (s, 3H), 4.12 (s, 2H), 7.762-7.874 (m, 3H), 7.979-7.984 (m, 1H); LC-MS (ESI) m/z 256.9 [M+H]+. extracted with EtOAc The reaction mixture was concentrated in vacuo purified by column chromatography on silica gel using 0-30% EtOAc in hexane