3-amino-2-methylbenzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 39 g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C. the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C.

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

Procedure: 3-amino-2-methylbenzonitrile (108 mg, 0.82 mmol) was reacted with 8-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (100 mg, 0.20 mmol) using an analogous procedure to the one described in Example 3.03 to give 8-(1-(3-cyano-2-methylphenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (52 mg, 55%) as a white solid. Mass Spectrum: M+H+ 461.

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

Procedure: 39 g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C. the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C.

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

Procedure: 39 g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C. the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off an the evaporation of the solvent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colourless flakes were obtained, with a melting point of 160° C.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 3-amino-2-methylbenzonitrile (4.32 g, 32.7 mmol), benzyl carbonochloridate (7.26 mL, 49.0 mmol), and potassium carbonate (6.78 g, 79.0 mmol) in tetrahydrofuran (280 mL) was stirred at room temperature for 3 days. The insoluble material was removed by filtration, and the filtrate was concentrated under vacuum. The residue was diluted with ethyl acetate (250 mL), washed with 1N HCl solution (60 mL), water (60 mL), and brine (60 mL). The organic solution was dried over anhydrous MgSO4, and the solution was concentrated under vacuum to dryness. The residue was stirred with hexane (100 mL) at room temperature for 1 hr. The insoluble product (6.41 g, 24.07 mmol, 73.6% yield) was collected as a white solid by suction filtration. The insoluble material was removed by filtration the filtrate was concentrated under vacuum The residue was diluted with ethyl acetate (250 mL) washed with 1N HCl solution (60 mL), water (60 mL), and brine (60 mL) The organic solution was dried over anhydrous MgSO4 the solution was concentrated under vacuum to dryness The residue was stirred with hexane (100 mL) at room temperature for 1 hr

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

Procedure: To a mixture of 2-methyl-3-nitrobenzonitrile (5.50 g, 33.9 mmol) and ammonium chloride (25.4 g, 475 mmol) in tetrahydrofuran (100 mL) and methanol (100 mL) at 0° C. was added zinc dust (31.1 g, 475 mmol) in portions. The mixture was stirred at room temperature for 2 hr. The insoluble material was removed by suction filtration through CELITE®, and the filtrate was concentrated under vacuum. The residue was diluted with water (50 mL) and extracted with CH2Cl2 (4×100 mL). The combined extract was dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (4.19 g, 31.7 mmol, 93% yield) as a white solid. The insoluble material was removed by suction filtration through CELITE® the filtrate was concentrated under vacuum The residue was diluted with water (50 mL) extracted with CH2Cl2 (4×100 mL) The combined extract was dried over anhydrous MgSO4 Removal of solvent under vacuum

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

Procedure: 39g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off and the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l

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

Procedure: 39g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off and the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l

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

Procedure: 39g (0.3 mole) of 2-methyl-3-amino-benzonitrile were dissolved in 75 ml of acetic acid, 30 ml (0.3 mole) of acetic anhydride were added, the mixture was heated with reflux for 5 minutes, and cooled. The solid obtained was filtered off and the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one. After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l the mixture was heated with reflux for 5 minutes cooled The solid obtained was filtered off the evaporation of the solent furnished an additional quantity of solid which was added to the preceding one After recrystallisation of the whole from toluene, 44 g (95%) of colorless flakes were obtained, with a melting point of 160° C. l

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

Procedure: 3-amino-2-methylbenzonitrile (108 mg, 0.82 mmol) was reacted with 8-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (100 mg, 0.20 mmol) using an analogous procedure to the one described in Example 3.03 to give 8-(1-(3-cyano-2-methylphenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (52 mg, 55%) as a white solid. Mass Spectrum: M+H+ 461.