2-amino-4-chloro-5-fluorobenzaldehyde

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-chloro-5-fluorobenzaldehyde (0.30 g, 1.73 mmol) and urea (1.04 g, 17.3 mmol) was heated to 180° C. for 1 h, then cooled to RT. The solid was then suspended in a mixture of EtOAc and water and then it was filtered and the collected solid was washed with water several times, then air-dried. This intermediate quinazolinone was then suspended in phosphorus oxychloride (3.0 mL, 32.2 mmol) and then heated to 100° C. for 1 h. After cooling to RT, the mixture was added dropwise to an ice-water mixture. The mixture was stirred for 5 minutes and then the product was extracted into EtOAc (3×). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 2,7-dichloro-6-fluoroquinazoline as a white solid (46 mg, 12% yield). m/z=217 (M+1). cooled to RT it was filtered the collected solid was washed with water several times air-dried heated to 100° C. for 1 h After cooling to RT the product was extracted into EtOAc (3×) The combined extracts were dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give an oil that was purified by silica gel chromatography

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

Procedure: A mixture of 4-chloro-5-fluoro-2-nitrobenzaldehyde (1.50 g, 7.37 mmol), concentrated hydrochloric acid (0.30 ml, 3.68 mmol), and iron (1.32 g, 23.6 mmol) in EtOH (18 mL), AcOH (18 mL), and water (9 mL) was heated to reflux for 30 minutes, then cooled to RT. The resulting suspension was filtered through CELITE™ and the filtrate was then partitioned between EtOAc and water. The layers were separated, the organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-amino-4-chloro-5-fluorobenzaldehyde as a yellow solid (1.15 g, 90% yield). m/z=174 (M+1). was heated to reflux for 30 minutes The resulting suspension was filtered through CELITE™ the filtrate was then partitioned between EtOAc and water The layers were separated the organic layer was washed with saturated aqueous sodium bicarbonate solution dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: A mixture of 4-chloro-5-fluoro-2-nitrobenzaldehyde (1.50 g, 7.37 mmol), concentrated hydrochloric acid (0.30 ml, 3.68 mmol), and iron (1.32 g, 23.6 mmol) in EtOH (18 mL), AcOH (18 mL), and water (9 mL) was heated to reflux for 30 minutes, then cooled to RT. The resulting suspension was filtered through CELITE™ and the filtrate was then partitioned between EtOAc and water. The layers were separated, the organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-amino-4-chloro-5-fluorobenzaldehyde as a yellow solid (1.15 g, 90% yield). m/z=174 (M+1). was heated to reflux for 30 minutes The resulting suspension was filtered through CELITE™ the filtrate was then partitioned between EtOAc and water The layers were separated the organic layer was washed with saturated aqueous sodium bicarbonate solution dried over anhydrous magnesium sulfate filtered concentrated in vacuo

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-chloro-5-fluorobenzaldehyde (0.30 g, 1.73 mmol) and urea (1.04 g, 17.3 mmol) was heated to 180° C. for 1 h, then cooled to RT. The solid was then suspended in a mixture of EtOAc and water and then it was filtered and the collected solid was washed with water several times, then air-dried. This intermediate quinazolinone was then suspended in phosphorus oxychloride (3.0 mL, 32.2 mmol) and then heated to 100° C. for 1 h. After cooling to RT, the mixture was added dropwise to an ice-water mixture. The mixture was stirred for 5 minutes and then the product was extracted into EtOAc (3×). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 2,7-dichloro-6-fluoroquinazoline as a white solid (46 mg, 12% yield). m/z=217 (M+1). cooled to RT it was filtered the collected solid was washed with water several times air-dried heated to 100° C. for 1 h After cooling to RT the product was extracted into EtOAc (3×) The combined extracts were dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give an oil that was purified by silica gel chromatography

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-chloro-5-fluorobenzaldehyde (0.30 g, 1.73 mmol) and urea (1.04 g, 17.3 mmol) was heated to 180° C. for 1 h, then cooled to RT. The solid was then suspended in a mixture of EtOAc and water and then it was filtered and the collected solid was washed with water several times, then air-dried. This intermediate quinazolinone was then suspended in phosphorus oxychloride (3.0 mL, 32.2 mmol) and then heated to 100° C. for 1 h. After cooling to RT, the mixture was added dropwise to an ice-water mixture. The mixture was stirred for 5 minutes and then the product was extracted into EtOAc (3×). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 2,7-dichloro-6-fluoroquinazoline as a white solid (46 mg, 12% yield). m/z=217 (M+1). cooled to RT it was filtered the collected solid was washed with water several times air-dried heated to 100° C. for 1 h After cooling to RT the product was extracted into EtOAc (3×) The combined extracts were dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give an oil that was purified by silica gel chromatography

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

Procedure: A mixture of 4-chloro-5-fluoro-2-nitrobenzaldehyde (1.50 g, 7.37 mmol), concentrated hydrochloric acid (0.30 ml, 3.68 mmol), and iron (1.32 g, 23.6 mmol) in EtOH (18 mL), AcOH (18 mL), and water (9 mL) was heated to reflux for 30 minutes, then cooled to RT. The resulting suspension was filtered through CELITE™ and the filtrate was then partitioned between EtOAc and water. The layers were separated, the organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-amino-4-chloro-5-fluorobenzaldehyde as a yellow solid (1.15 g, 90% yield). m/z=174 (M+1). was heated to reflux for 30 minutes The resulting suspension was filtered through CELITE™ the filtrate was then partitioned between EtOAc and water The layers were separated the organic layer was washed with saturated aqueous sodium bicarbonate solution dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: A mixture of 4-chloro-5-fluoro-2-nitrobenzaldehyde (1.50 g, 7.37 mmol), concentrated hydrochloric acid (0.30 ml, 3.68 mmol), and iron (1.32 g, 23.6 mmol) in EtOH (18 mL), AcOH (18 mL), and water (9 mL) was heated to reflux for 30 minutes, then cooled to RT. The resulting suspension was filtered through CELITE™ and the filtrate was then partitioned between EtOAc and water. The layers were separated, the organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-amino-4-chloro-5-fluorobenzaldehyde as a yellow solid (1.15 g, 90% yield). m/z=174 (M+1). was heated to reflux for 30 minutes The resulting suspension was filtered through CELITE™ the filtrate was then partitioned between EtOAc and water The layers were separated the organic layer was washed with saturated aqueous sodium bicarbonate solution dried over anhydrous magnesium sulfate filtered concentrated in vacuo

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-chloro-5-fluorobenzaldehyde (0.30 g, 1.73 mmol) and urea (1.04 g, 17.3 mmol) was heated to 180° C. for 1 h, then cooled to RT. The solid was then suspended in a mixture of EtOAc and water and then it was filtered and the collected solid was washed with water several times, then air-dried. This intermediate quinazolinone was then suspended in phosphorus oxychloride (3.0 mL, 32.2 mmol) and then heated to 100° C. for 1 h. After cooling to RT, the mixture was added dropwise to an ice-water mixture. The mixture was stirred for 5 minutes and then the product was extracted into EtOAc (3×). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 2,7-dichloro-6-fluoroquinazoline as a white solid (46 mg, 12% yield). m/z=217 (M+1). cooled to RT it was filtered the collected solid was washed with water several times air-dried heated to 100° C. for 1 h After cooling to RT the product was extracted into EtOAc (3×) The combined extracts were dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give an oil that was purified by silica gel chromatography

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

Procedure: A mixture of 4-chloro-5-fluoro-2-nitrobenzaldehyde (1.50 g, 7.37 mmol), concentrated hydrochloric acid (0.30 ml, 3.68 mmol), and iron (1.32 g, 23.6 mmol) in EtOH (18 mL), AcOH (18 mL), and water (9 mL) was heated to reflux for 30 minutes, then cooled to RT. The resulting suspension was filtered through CELITE™ and the filtrate was then partitioned between EtOAc and water. The layers were separated, the organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-amino-4-chloro-5-fluorobenzaldehyde as a yellow solid (1.15 g, 90% yield). m/z=174 (M+1). was heated to reflux for 30 minutes The resulting suspension was filtered through CELITE™ the filtrate was then partitioned between EtOAc and water The layers were separated the organic layer was washed with saturated aqueous sodium bicarbonate solution dried over anhydrous magnesium sulfate filtered concentrated in vacuo