1,4-difluoro-2-isocyanatobenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3d was prepared from 2,5-difluorophenyl isocyanate and compound 2a using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3d was prepared from 2,5-difluorophenyl isocyanate and compound 2a using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3c was prepared from 2,5-difluorophenyl isocyanate and compound 2b, using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3c was prepared from 2,5-difluorophenyl isocyanate and compound 2b, using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,5-Difluorophenylisocyanate (1.55 g, 10.0 mmol) in methylene chloride (25 mL) was added dropwise to a suspension of phenylalanine (1.65 g, 10.0 mmol) in methylene chloride (50 mL) containing triethylamine (1.4 mL, 1.01 g, 10.0 mmol). The solution was allowed to stir overnight, and was then concentrated. The residue was taken up into 6N HCl and heated to reflux for 3 hours. The cooled solution was extracted with ethyl acetate (3×), and the combined extracts were washed with water (2×), dried (over MgSO4), filtered and concentrated to give 2.7 grams. Purification by column chromatography gave 2.5 grams of 5-benzyl-3-(2.5-difluorophenyl)imidazolidine-2,4-dione. was then concentrated heated to reflux for 3 hours The cooled solution was extracted with ethyl acetate (3×) the combined extracts were washed with water (2×) dried (over MgSO4) filtered concentrated to give 2.7 grams Purification by column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,5-Difluorophenylisocyanate (1.55 g, 10.0 mmol) in methylene chloride (25 mL) was added dropwise to a suspension of phenylalanine (1.65 g, 10.0 mmol) in methylene chloride (50 mL) containing triethylamine (1.4 mL, 1.01 g, 10.0 mmol). The solution was allowed to stir overnight, and was then concentrated. The residue was taken up into 6N HCl and heated to reflux for 3 hours. The cooled solution was extracted with ethyl acetate (3×), and the combined extracts were washed with water (2×), dried (over MgSO4), filtered and concentrated to give 2.7 grams. Purification by column chromatography gave 2.5 grams of 5-benzyl-3-(2.5-difluorophenyl)imidazolidine-2,4-dione. was then concentrated heated to reflux for 3 hours The cooled solution was extracted with ethyl acetate (3×) the combined extracts were washed with water (2×) dried (over MgSO4) filtered concentrated to give 2.7 grams Purification by column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3d was prepared from 2,5-difluorophenyl isocyanate and compound 2a using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 3c was prepared from 2,5-difluorophenyl isocyanate and compound 2b, using the method described in Example 9. MS (EI)=444 (M+).

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (100 mg) was dissolved in toluene (10 ml) with heat, 2,5-difluorophenyl isocyanate (120 μl) was added, and the admixture was refluxed with heat for 30 minutes. The separated crystals were filtered and then washed with toluene to obtain 132 mg of the title compound (yield: 87%). with heat the admixture was refluxed with heat for 30 minutes The separated crystals were filtered washed with toluene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound A6 (0.50 g, 1.18 mmol) was dissolved in DCM (3 mL) and combined with trifluoroacetic acid (3 mL). The reaction mixture was stirred for 5 min at RT and the solvent was then removed under a vacuum. The residue was combined repeatedly with toluene and the solvent was then removed again. The residue was then combined with sat. aq. NaHCO3 solution and repeatedly extracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was removed under a vacuum. The residue was redissolved in anhydrous THF (5 mL) and combined with a little triethylamine. The reaction mixture was combined with 2,5-difluorophenyl isocyanate (145 μL, 1.23 mmol), stirred for 18 h at RT and combined with water and EtOAc. The organic phase was separated off and the aqueous phase repeatedly extracted with EtOAc. The combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. The residue was purified by column chromatography (SiO2, heptane/EtOAc 2:1). After crystallisation from heptane and DCM, 483 mg (85% of theoretical) of the desired product 3-(3-bromobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid (2,5-difluorophenyl)amide (29) were obtained. the solvent was then removed under a vacuum the solvent was then removed again repeatedly extracted with EtOAc The combined organic phases were dried over Na2SO4 the solvent was removed under a vacuum The residue was redissolved in anhydrous THF (5 mL) stirred for 18 h at RT The organic phase was separated off the aqueous phase repeatedly extracted with EtOAc The combined organic phases were washed with sat. aq. NaCl solution dried over Na2SO4 the solvent was removed under a vacuum The residue was purified by column chromatography (SiO2, heptane/EtOAc 2:1) After crystallisation from heptane and DCM, 483 mg (85% of theoretical) of the desired product 3-(3-bromobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid (2,5-difluorophenyl)amide (29) were obtained