3-methyl-5H-2,3-benzodiazepin-4-one

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: To a well stirred solution of 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one (3.0 g, 17.2 mmol) in anhydrous tetrahydrofuran (100 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (45 mL, 22.4 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (5.8 g, 19 mmol) in THF (0.4M) via a cannula over a period of 2 min (Evans et al., J. Amer. Chem. Soc. 1990, 112, 4011–4030; Butcher et al., Tetrahedron Lett., 1996, 37(37), 6685–6688). After 5 min, acetic acid (4.9 mL, 86 mmol) was added and stirring continued for another 6 h. The reaction mixture was diluted with EtOAc (300 mL), washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL). The solvent was removed and the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 75% yield. After 5 min stirring continued for another 6 h washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL) The solvent was removed the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica)

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

実験手順: To a solution of o-formylphenylacetic acid (10 g, 61 mmol) (Bleasdale et al., J. Chem. Soc. Perkin Trans. I 1991, 1683) in 60 mL of EtOH was added N-methylhydrazine (4.2 g, 91 mmol) and refluxed for 1 h. The reaction mixture cooled, solvent removed and transferred the crude reaction mixture to a vaccum sublimation apparatus. The imine was heated at 140° C. under high vaccum for 1 h and collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091). The product was crystallized from 20% ethyl acetate in hexane. 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was obtained in 50% yield. refluxed for 1 h The reaction mixture cooled solvent removed reaction mixture to a vaccum sublimation apparatus collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091) The product was crystallized from 20% ethyl acetate in hexane

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

実験手順: To a solution of o-formylphenylacetic acid (10 g, 61 mmol) (Bleasdale et al., J. Chem. Soc. Perkin Trans. I 1991, 1683) in 60 mL of EtOH was added N-methylhydrazine (4.2 g, 91 mmol) and refluxed for 1 h. The reaction mixture cooled, solvent removed and transferred the crude reaction mixture to a vaccum sublimation apparatus. The imine was heated at 140° C. under high vaccum for 1 h and collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091). The product was crystallized from 20% ethyl acetate in hexane. 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was obtained in 50% yield. refluxed for 1 h The reaction mixture cooled solvent removed reaction mixture to a vaccum sublimation apparatus collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091) The product was crystallized from 20% ethyl acetate in hexane

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: To a well stirred solution of 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one (3.0 g, 17.2 mmol) in anhydrous tetrahydrofuran (100 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (45 mL, 22.4 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (5.8 g, 19 mmol) in THF (0.4M) via a cannula over a period of 2 min (Evans, et al., J. Amer. Chem. Soc., 1990, 112, 4011-4030; Butcher, et al., Tetrahedron Lett., 1996, 37 (37), 6685-6688). After 5 min, acetic acid (4.9 mL, 86 mmol) was added and stirring continued for another 6 h. The reaction mixture was diluted with EtOAc (300 mL), washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL). The solvent was removed and the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 75% yield. After 5 min stirring continued for another 6 h washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL) The solvent was removed the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica)

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

実験手順: To a solution of ortho-formylphenylacetic acid (10 g, 61 mmol) (Bleasdale, et al., J. Chem. Soc. Perkin Trans., 1991, 1683) in 60 mL of EtOH was added N-methylhydrazine (4.2 g, 91 mmol) and refluxed for 1 h. The reaction mixture cooled, solvent removed and transferred the crude reaction mixture to a vacuum sublimation apparatus. The imine was heated at 140° C. under high vacuum for 1 h and collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan, et al., J. Med. Chem., 1972, 15 (10), 1091). The product was crystallized from 20% ethyl acetate in hexane. 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was obtained in 50% yield. refluxed for 1 h The reaction mixture cooled solvent removed reaction mixture to a vacuum sublimation apparatus collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan, et al., J. Med. Chem., 1972, 15 (10), 1091) The product was crystallized from 20% ethyl acetate in hexane

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

実験手順: To a well stirred solution of 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one (3.0 g, 17.2 mmol) in anhydrous tetrahydrofuran (100 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (45 mL, 22.4 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (5.8 g, 19 mmol) in THF (0.4M) via a cannula over a period of 2 min (Evans et al., J. Amer. Chem. Soc. 1990, 112, 4011–4030; Butcher et al., Tetrahedron Lett., 1996, 37(37), 6685–6688). After 5 min, acetic acid (4.9 mL, 86 mmol) was added and stirring continued for another 6 h. The reaction mixture was diluted with EtOAc (300 mL), washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL). The solvent was removed and the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 75% yield. After 5 min stirring continued for another 6 h washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL) The solvent was removed the 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica)

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

実験手順: To a solution of o-formylphenylacetic acid (10 g, 61 mmol) (Bleasdale et al., J. Chem. Soc. Perkin Trans. I 1991, 1683) in 60 mL of EtOH was added N-methylhydrazine (4.2 g, 91 mmol) and refluxed for 1 h. The reaction mixture cooled, solvent removed and transferred the crude reaction mixture to a vaccum sublimation apparatus. The imine was heated at 140° C. under high vaccum for 1 h and collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091). The product was crystallized from 20% ethyl acetate in hexane. 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was obtained in 50% yield. refluxed for 1 h The reaction mixture cooled solvent removed reaction mixture to a vaccum sublimation apparatus collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan et al., J. Med. Chem., 1972, 15(10), 1091) The product was crystallized from 20% ethyl acetate in hexane