1-(3-chloro-4-fluorophenyl)-2-phenylethanone

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE: EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE: EtOAc=100:1)

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

Procedure: To a solution of 1-(3-chloro-4-fluorophenyl)-2-phenylethanone (Intermediate 17) (65 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (51.6 mg, 0.26 mmol), and urea (47.6 mg, 0.78 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 44 (22 mg, yield 17.4%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.43 (m, 2H), 7.28 (t, J=9.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.87 (d, J=6.3 Hz, 2H), 5.25 (d, J=2.4 Hz, 1H), 4.04 (m, 2H), 1.32 (t, J=6.9 Hz, 3H); MS (ESI): m/z 483.9 [M+1]+. the mixture was refluxed for 2 days After the solvent was removed under reduced pressure the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE:EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE:EtOAc=100:1)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE:EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE:EtOAc=100:1)

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

Procedure: To a solution of 1-(3-chloro-4-fluorophenyl)-2-phenylethanone (Intermediate 17) (65 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (51.6 mg, 0.26 mmol), and urea (47.6 mg, 0.78 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 44 (22 mg, yield 17.4%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.43 (m, 2H), 7.28 (t, J=9.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.87 (d, J=6.3 Hz, 2H), 5.25 (d, J=2.4 Hz, 1H), 4.04 (m, 2H), 1.32 (t, J=6.9 Hz, 3H); MS (ESI): m/z 483.9[M+1]+. the mixture was refluxed for 2 days After the solvent was removed under reduced pressure the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE: EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE: EtOAc=100:1)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE: EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE: EtOAc=100:1)

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

Procedure: To a solution of 1-(3-chloro-4-fluorophenyl)-2-phenylethanone (Intermediate 17) (65 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (51.6 mg, 0.26 mmol), and urea (47.6 mg, 0.78 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 44 (22 mg, yield 17.4%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.43 (m, 2H), 7.28 (t, J=9.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.87 (d, J=6.3 Hz, 2H), 5.25 (d, J=2.4 Hz, 1H), 4.04 (m, 2H), 1.32 (t, J=6.9 Hz, 3H); MS (ESI): m/z 483.9 [M+1]+. the mixture was refluxed for 2 days After the solvent was removed under reduced pressure the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

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

Procedure: To a solution of 1-(3-chloro-4-fluorophenyl)-2-phenylethanone (Intermediate 17) (65 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (51.6 mg, 0.26 mmol), and urea (47.6 mg, 0.78 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 44 (22 mg, yield 17.4%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.43 (m, 2H), 7.28 (t, J=9.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.87 (d, J=6.3 Hz, 2H), 5.25 (d, J=2.4 Hz, 1H), 4.04 (m, 2H), 1.32 (t, J=6.9 Hz, 3H); MS (ESI): m/z 483.9 [M+1]+. the mixture was refluxed for 2 days After the solvent was removed under reduced pressure the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE:EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE:EtOAc=100:1)

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

Procedure: Prepared following the procedure described in Intermediate 13, starting from 4-bromo-2-chloro-1-fluorobenzene, where the crude product was purified by column chromatography (PE:EtOAc=100:1) to afford Intermediate 17 (110 mg, yield 20.0%). Prepared was purified by column chromatography (PE:EtOAc=100:1)

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

Procedure: To a solution of 1-(3-chloro-4-fluorophenyl)-2-phenylethanone (Intermediate 17) (65 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (51.6 mg, 0.26 mmol), and urea (47.6 mg, 0.78 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 44 (22 mg, yield 17.4%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.43 (m, 2H), 7.28 (t, J=9.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.87 (d, J=6.3 Hz, 2H), 5.25 (d, J=2.4 Hz, 1H), 4.04 (m, 2H), 1.32 (t, J=6.9 Hz, 3H); MS (ESI): m/z 483.9[M+1]+. the mixture was refluxed for 2 days After the solvent was removed under reduced pressure the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)