3-formyl-2-hydroxybenzonitrile

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 1,2-diphenylethanone (1.6 g, 8.16 mmol), and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) (1.0 g, 6.80 mmol) in AcOH (5 mL) was added urea (1.2 g, 20.4 mmol). The mixture was stirred at 120° C. under microwave for 3 h. The volatiles were removed under reduced pressure and standard aqueous workup procedure was followed. The crude was recrystallized by EA (10 mL) to afford Compound 94 as a white power (436 mg, 26%). 1H NMR (DMSO-d6 500 MHz): δ 8.10 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 3H), 7.30-7.36 (m, 3H), 7.18 (s, 1H), 7.02 (d, J=6.0 Hz, 3H), 6.78 (d, J=6.0 Hz, 2H), 4.44 (d, J=2.0 Hz, 1H), 4.14 (s, 1H); MS (ESI): m/z 368.1 [M+1]+. The volatiles were removed under reduced pressure and standard aqueous workup procedure The crude was recrystallized by EA (10 mL)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 1,2-diphenylethanone (1.6 g, 8.16 mmol), and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) (1.0 g, 6.80 mmol) in AcOH (5 mL) was added urea (1.2 g, 20.4 mmol). The mixture was stirred at 120° C. under microwave for 3 h. The volatiles were removed under reduced pressure and standard aqueous workup procedure was followed. The crude was recrystallized by EA (10 mL) to afford Compound 94 as a white power (436 mg, 26%). 1H NMR (DMSO-d6500 MHz): δ 8.10 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 3H), 7.30-7.36 (m, 3H), 7.18 (s, 1H), 7.02 (d, J=6.0 Hz, 3H), 6.78 (d, J=6.0 Hz, 2H), 4.44 (d, J=2.0 Hz, 1H), 4.14 (s, 1H); MS (ESI): m/z 368.1 [M+1]+. The volatiles were removed under reduced pressure and standard aqueous workup procedure The crude was recrystallized by EA (10 mL)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 1,2-diphenylethanone (1.6 g, 8.16 mmol), and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) (1.0 g, 6.80 mmol) in AcOH (5 mL) was added urea (1.2 g, 20.4 mmol). The mixture was stirred at 120° C. under microwave for 3 h. The volatiles were removed under reduced pressure and standard aqueous workup procedure was followed. The crude was recrystallized by EA (10 mL) to afford Compound 94 as a white power (436 mg, 26%). 1H NMR (DMSO-d6 500 MHz): δ 8.10 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 3H), 7.30-7.36 (m, 3H), 7.18 (s, 1H), 7.02 (d, J=6.0 Hz, 3H), 6.78 (d, J=6.0 Hz, 2H), 4.44 (d, J=2.0 Hz, 1H), 4.14 (s, 1H); MS (ESI): m/z 368.1 [M+1]+. The volatiles were removed under reduced pressure and standard aqueous workup procedure The crude was recrystallized by EA (10 mL)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 1,2-diphenylethanone (1.6 g, 8.16 mmol), and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) (1.0 g, 6.80 mmol) in AcOH (5 mL) was added urea (1.2 g, 20.4 mmol). The mixture was stirred at 120° C. under microwave for 3 h. The volatiles were removed under reduced pressure and standard aqueous workup procedure was followed. The crude was recrystallized by EA (10 mL) to afford Compound 94 as a white power (436 mg, 26%). 1H NMR (DMSO-d6500 MHz): δ 8.10 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 3H), 7.30-7.36 (m, 3H), 7.18 (s, 1H), 7.02 (d, J=6.0 Hz, 3H), 6.78 (d, J=6.0 Hz, 2H), 4.44 (d, J=2.0 Hz, 1H), 4.14 (s, 1H); MS (ESI): m/z 368.1 [M+1]+. The volatiles were removed under reduced pressure and standard aqueous workup procedure The crude was recrystallized by EA (10 mL)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)

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

Procedure: To a solution of 1,2-diphenylethanone (1.6 g, 8.16 mmol), and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) (1.0 g, 6.80 mmol) in AcOH (5 mL) was added urea (1.2 g, 20.4 mmol). The mixture was stirred at 120° C. under microwave for 3 h. The volatiles were removed under reduced pressure and standard aqueous workup procedure was followed. The crude was recrystallized by EA (10 mL) to afford Compound 94 as a white power (436 mg, 26%). 1H NMR (DMSO-d6500 MHz): δ 8.10 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 3H), 7.30-7.36 (m, 3H), 7.18 (s, 1H), 7.02 (d, J=6.0 Hz, 3H), 6.78 (d, J=6.0 Hz, 2H), 4.44 (d, J=2.0 Hz, 1H), 4.14 (s, 1H); MS (ESI): m/z 368.1 [M+1]+. The volatiles were removed under reduced pressure and standard aqueous workup procedure The crude was recrystallized by EA (10 mL)

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

Procedure: To a solution of 2-hydroxybenzonitrile (4.70 g, 41.6 mmol) in acetic acid (40 mL) was added hexamethylenetetraamine (8.7 g, 62.4 mmol) and the mixture was heated to 120° C. for 2 h. The mixture was cooled to room temperature, followed by a standard aqueous/EtOAc workup and purified by silica gel column chromatography (PE:EA=1:1) to afford 5-formyl-2-hydroxybenzonitrile (Intermediate 47a) as a white powder (540 mg, 9%) and 3-formyl-2-hydroxybenzonitrile (Intermediate 47b) as a white powder (1.17 g, 19%). The mixture was cooled to room temperature purified by silica gel column chromatography (PE:EA=1:1)