3-ethoxy-5-fluoro-4-hydroxybenzaldehyde

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: The mixture of 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (Intermediate 32) (160 mg, 0.87 mmol), 1,2-diphenyl-ethanone (170 mg, 0.87 mmol), urea (157 mg, 2.61 mmol), and concentrated HCl solution (0.2 mL) in ethanol (20 mL) was degassed and refluxed for 3 days under N2 protection. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to give Compound 64 (30 mg, 10.6%). 1H NMR (DMSO-d6 300 MHz) δ 9.08 (s, br, 1H), 8.63 (s, 1H), 7.42 (s, 1H), 7.19-7.26 (m, 5H), 7.01-7.03 (m, 3H), 6.72-6.81 (m, 4H), 5.04 (d, J=2.7 Hz, 1H), 3.99 (q, J1=6.9 Hz, J2=9.0 Hz, 2H), 1.33 (t, J=6.9 Hz, 3H); MS (ESI): m/z 405.1 [M+1]+. was degassed refluxed for 3 days under N2 protection The solvent was removed under reduced pressure the residue was purified by preparative HPLC

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel

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

Procedure: To the solution of 3,4-diethoxy-5-fluorobenzaldehyde (300 mg, 1.4 mmol) in DCM (50 mL) was added AlCl3 (207 mg, 1.55 mmol), and at 0° C., pyridine (230 mg, 2.8 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was cooled to room temperature, poured into ice water solution, and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give 3-ethoxy-5-fluoro-4-hydroxybenzaldehyde (160 mg). the resulting mixture was refluxed overnight extracted with EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure purified by column chromatography on silica gel