1-(2-aminophenyl)butan-1-one

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

Procedure: A slurry of 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine (1.1 equiv.; Katritzky, A. R.; Urogdi, L.; Mayence, A. J. Org. Chem. 1990, 55, 2206) in THF (0.3 M) was cooled to 0° C. and treated with oxalyl chloride (1.1 equiv.) in a dropwise manner. To the slurry was added dropwise DMF (0.1 equiv.); stirring was continued at 0° C. for 1 hour. A solution of 1-(2-aminophenyl)-1-butanone and N-methylmorpholine (2.2 equiv.) in THF (1 M in butanone), pre-cooled to 0° C., was added via cannula. Upon completion of the addition, the reaction was warmed to ambient temperature. The mixture was filtered, washing the filter cake with THF. The filtrate was transferred to a three-neck flask and treated with ammonia gas through a dispersion tube for 15 minutes. Methanol (0.3 M in butanone) was added and the ammonia continued to be bubbled through the solution for 1 hour. The reaction was concentrated, diluted with ethyl acetate, and re-concentrated; this was repeated again. The residue was diluted with ethyl acetate and washed twice with 1 N NaOH. The aqueous washes were back-extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. Acetic acid was added and concentrated in vacuo. The syrup was dissolved in acetic acid (0.6 M in butanone) and treated with ammonium acetate (4.0 equiv.). The reaction was stirred at ambient temperature for 18 hours. The resultant solid was filtered, washing with H2O. was added via cannula Upon completion of the addition The mixture was filtered washing the filter cake with THF The filtrate was transferred to a three-neck flask treated with ammonia gas through a dispersion tube for 15 minutes Methanol (0.3 M in butanone) was added to be bubbled through the solution for 1 hour The reaction was concentrated diluted with ethyl acetate re-concentrated The residue was diluted with ethyl acetate washed twice with 1 N NaOH The aqueous washes were back-extracted with ethyl acetate The combined organics were washed with brine dried over Na2SO4 filtered concentrated Acetic acid was added concentrated in vacuo The syrup was dissolved in acetic acid (0.6 M in butanone) The reaction was stirred at ambient temperature for 18 hours The resultant solid was filtered washing with H2O

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

Procedure: A slurry of 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine (1.1 equiv.; Katritzky, A. R.; Urogdi, L.; Mayence, A. J. Org. Chem. 1990, 55, 2206) in THF (0.3 M) was cooled to 0° C. and treated with oxalyl chloride (1.1 equiv.) in a dropwise manner. To the slurry was added dropwise DMF (0.1 equiv.); stirring was continued at 0° C. for 1 hour. A solution of 1-(2-aminophenyl)-1-butanone and N-methylmorpholine (2.2 equiv.) in THF (1 M in butanone), pre-cooled to 0° C., was added via cannula. Upon completion of the addition, the reaction was warmed to ambient temperature. The mixture was filtered, washing the filter cake with THF. The filtrate was transferred to a three-neck flask and treated with ammonia gas through a dispersion tube for 15 minutes. Methanol (0.3 M in butanone) was added and the ammonia continued to be bubbled through the solution for 1 hour. The reaction was concentrated, diluted with ethyl acetate, and re-concentrated; this was repeated again. The residue was diluted with ethyl acetate and washed twice with 1 N NaOH. The aqueous washes were back-extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. Acetic acid was added and concentrated in vacuo. The syrup was dissolved in acetic acid (0.6 M in butanone) and treated with ammonium acetate (4.0 equiv.). The reaction was stirred at ambient temperature for 18 hours. The resultant solid was filtered, washing with H2O. was added via cannula Upon completion of the addition The mixture was filtered washing the filter cake with THF The filtrate was transferred to a three-neck flask treated with ammonia gas through a dispersion tube for 15 minutes Methanol (0.3 M in butanone) was added to be bubbled through the solution for 1 hour The reaction was concentrated diluted with ethyl acetate re-concentrated The residue was diluted with ethyl acetate washed twice with 1 N NaOH The aqueous washes were back-extracted with ethyl acetate The combined organics were washed with brine dried over Na2SO4 filtered concentrated Acetic acid was added concentrated in vacuo The syrup was dissolved in acetic acid (0.6 M in butanone) The reaction was stirred at ambient temperature for 18 hours The resultant solid was filtered washing with H2O

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

Procedure: A solution of anthranilonitrile (1 equiv., Aldrich) in diethyl ether (2.4 M) was cooled to 0° C. and treated with propylmagnesium chloride (2.5 equiv., Aldrich; 2.0 M in Et2O) in a dropwise manner over the course of an hour. After addition of 25% of the Grignard reagent, an additional 1/10 volume of Et2O was added. The cooling bath was removed and stirring of the suspension continued for 5 hours. The reaction was returned to 0° C. and cautiously quenched with 3 N HCl. The cooling bath was removed and stirring continued for 30 minutes. The mixture was made basic by the addition of solid NaOH. The contents were extracted thrice with ethyl acetate; brine was added to help break up the suspension. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was chromatographed eluting with 95:5 hexanes/ethyl acetate. The cooling bath was removed was returned to 0° C. cautiously quenched with 3 N HCl The cooling bath was removed stirring continued for 30 minutes The mixture was made basic by the addition of solid NaOH The contents were extracted thrice with ethyl acetate brine was added The combined extracts were washed with brine dried over Na2SO4 filtered concentrated The crude residue was chromatographed eluting with 95:5 hexanes/ethyl acetate

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

Procedure: A slurry of 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine (1,1 equiv.; Katritzky, A. R. et al. J. Org. Chem. 1990, 55, 2206, incorporated herein by reference) in THF (0.3 M) was cooled to 0° C. and treated with oxalyl chloride (1.1 equiv.) in a dropwise manner. To the slurry was added dropwise DMF (0.1 equiv.); stirring was continued at 0° C. for 1 hour. A solution of 1-(2-aminophenyl)-1-butanone and N-methylmorpholine (2.2 equiv.) in THF (1 M in butanone), pre-cooled to 0° C., was added via cannula. Upon completion of the addition, the reaction was warmed to ambient temperature. The mixture was filtered, washing the filter cake with THF. The filtrate was transferred to a three-neck flask and treated with ammonia gas through a dispersion tube for 15 minutes. Methanol (0.3 M in butanone) was added and the ammonia continued to be bubbled through the solution for 1 hour. The reaction was concentrated, diluted with ethyl acetate, and re-concentrated; this was repeated again. The residue was diluted with ethyl acetate and washed twice with 1 N NaOH. The aqueous washes were back-extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. Acetic acid was added and concentrated in vacuo. The syrup was dissolved in acetic acid (0.6 M in butanone) and treated with ammonium acetate (4.0 equiv.). The reaction was stirred at ambient temperature for 18 hours. The resultant solid was filtered, washing with H2O. was added via cannula Upon completion of the addition The mixture was filtered washing the filter cake with THF The filtrate was transferred to a three-neck flask treated with ammonia gas through a dispersion tube for 15 minutes Methanol (0.3 M in butanone) was added to be bubbled through the solution for 1 hour The reaction was concentrated diluted with ethyl acetate re-concentrated The residue was diluted with ethyl acetate washed twice with 1 N NaOH The aqueous washes were back-extracted with ethyl acetate The combined organics were washed with brine dried over Na2SO4 filtered concentrated Acetic acid was added concentrated in vacuo The syrup was dissolved in acetic acid (0.6 M in butanone) The reaction was stirred at ambient temperature for 18 hours The resultant solid was filtered washing with H2O

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

Procedure: A solution of anthranilonitrile (1 equiv., Aldrich) in diethyl ether (2.4 M) was cooled to 0° C. and treated with propylmagnesium chloride (2.5 equiv., Aldrich; 2.0 M in Et2O) in a dropwise manner over the course of an hour. After addition of 25% of the Grignard reagent, an additional {fraction (1/10)} volume of Et2O was added. The cooling bath was removed and stirring of the suspension continued for 5 hours. The reaction was returned to 0° C. and cautiously quenched with 3 N HCl. The cooling bath was removed and stirring continued for 30 minutes. The mixture was made basic by the addition of solid NaOH. The contents were extracted thrice with ethyl acetate; brine was added to help break up the suspension. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was chromatographed eluting with 95:5 hexanes/ethyl acetate. The cooling bath was removed was returned to 0° C. cautiously quenched with 3 N HCl The cooling bath was removed stirring continued for 30 minutes The mixture was made basic by the addition of solid NaOH The contents were extracted thrice with ethyl acetate brine was added The combined extracts were washed with brine dried over Na2SO4 filtered concentrated The crude residue was chromatographed eluting with 95:5 hexanes/ethyl acetate

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

Procedure: A slurry of 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine (1.1 equiv.; Katritzky, A. R. et al. J. Org. Chem. 1990, 55, 2206, incorporated herein by reference) in THF (0.3 M) was cooled to 0° C. and treated with oxalyl chloride (1.1 equiv.) in a dropwise manner. To the slurry was added dropwise DMF (0.1 equiv.); stirring was continued at 0° C. for 1 hour. A solution of 1-(2-aminophenyl)-1-butanone and N-methylmorpholine (2.2 equiv.) in THF (1 M in butanone), pre-cooled to 0° C., was added via cannula. Upon completion of the addition, the reaction was warmed to ambient temperature. The mixture was filtered, washing the filter cake with THF. The filtrate was transferred to a three-neck flask and treated with ammonia gas through a dispersion tube for 15 minutes. Methanol (0.3 M in butanone) was added and the ammonia continued to be bubbled through the solution for 1 hour. The reaction was concentrated, diluted with ethyl acetate, and re-concentrated; this was repeated again. The residue was diluted with ethyl acetate and washed twice with 1 N NaOH. The aqueous washes were back-extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. Acetic acid was added and concentrated in vacuo. The syrup was dissolved in acetic acid (0.6 M in butanone) and treated with ammonium acetate (4.0 equiv.). The reaction was stirred at ambient temperature for 18 hours. The resultant solid was filtered, washing with H2O. was added via cannula Upon completion of the addition The mixture was filtered washing the filter cake with THF The filtrate was transferred to a three-neck flask treated with ammonia gas through a dispersion tube for 15 minutes Methanol (0.3 M in butanone) was added to be bubbled through the solution for 1 hour The reaction was concentrated diluted with ethyl acetate re-concentrated The residue was diluted with ethyl acetate washed twice with 1 N NaOH The aqueous washes were back-extracted with ethyl acetate The combined organics were washed with brine dried over Na2SO4 filtered concentrated Acetic acid was added concentrated in vacuo The syrup was dissolved in acetic acid (0.6 M in butanone) The reaction was stirred at ambient temperature for 18 hours The resultant solid was filtered washing with H2O