4-bromo-2-chloro-1-isocyanatobenzene

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

実験手順: To a stirred or shaken solution of 157 mg (0.76 mmol) of (4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine (abbreviated as (4S,5S)-amine 1) in pentane (3.5 mL) was added dropwise a solution of 169 mg (0.73 mmol) of 4-bromo-2-chlorophenyl isocyanate in dichloromethane (0.7 mL). A white precipitate was observed after stirring for 0.5 to 2 h. The precipitate was collected, rinsed with pentane, and dried under vacuum to yield 280 mg (88%) of the title compound. In some examples, pentane was used to dissolve the required isocyanate rather than dichloromethane. In addition, if the required isocyanate was a liquid, it was added dropwise as a neat liquid on small-scale reactions such as this. In cases where a precipitate was not observed or the precipitate was not of sufficient purity, the solvent was evaporated, and the residue was purified by column chromatography (hexanes/ethyl acetate) to yield the desired product. after stirring for 0.5 to 2 h The precipitate was collected rinsed with pentane dried under vacuum

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

実験手順: To a stirred or shaken solution of 157 mg (0.76 mmol) of (4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine (abbreviated as (4S,5S)-amine 1) in pentane (3.5 mL) was added dropwise a solution of 169 mg (0.73 mmol) of 4-bromo-2-chlorophenyl isocyanate in dichloromethane (0.7 mL). A white precipitate was observed after stirring for 0.5 to 2 h. The precipitate was collected, rinsed with pentane, and dried under vacuum to yield 280 mg (88%) of the title compound. In some examples, pentane was used to dissolve the required isocyanate rather than dichloromethane. In addition, if the required isocyanate was a liquid, it was added dropwise as a neat liquid on small-scale reactions such as this. In cases where a precipitate was not observed or the precipitate was not of sufficient purity, the solvent was evaporated, and the residue was purified by column chromatography (hexanes/ethyl acetate) to yield the desired product. after stirring for 0.5 to 2 h The precipitate was collected rinsed with pentane dried under vacuum

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

実験手順: To a solution of 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (700 mg, 3.31 mmol) in dry dichloromethane (15 mL) was added 4-bromo-2-chloro-1-isocyanatobenzene (770 mg, 3.31 mmol). The reaction was stirred overnight, diluted with hexane (15 mL), and the precipitate collected and washed with hexane to provide the title compound (1.3 g, 2.93 mmol, 88% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.85 (br. s, 1H), 8.82 (br. s, 1H), 8.50-8.23 (m, 1H), 8.05 (dd, J=5.3, 8.8 Hz, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 3.81 (dd, J=7.6, 9.9 Hz, 0.5H), 3.77-3.39 (m, 2H), 3.31-3.13 (m, 1H), 2.94 (d, J=19.5 Hz, 0.5H), 2.64-2.54 (m, 0.5H), 2.47-2.39 (m, 0.5H), 2.28 (dd, J=7.3, 16.7 Hz, 2H), 2.17-1.88 (m, 1H), 1.80-1.47 (m, 2H), 0.81-0.61 (m, 4H). the precipitate collected washed with 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 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (700 mg, 3.31 mmol) in dry dichloromethane (15 mL) was added 4-bromo-2-chloro-1-isocyanatobenzene (770 mg, 3.31 mmol). The reaction was stirred overnight, diluted with hexane (15 mL), and the precipitate collected and washed with hexane to provide the title compound (1.3 g, 2.93 mmol, 88% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.85 (br. s, 1H), 8.82 (br. s, 1H), 8.50-8.23 (m, 1H), 8.05 (dd, J=5.3, 8.8 Hz, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 3.81 (dd, J=7.6, 9.9 Hz, 0.5H), 3.77-3.39 (m, 2H), 3.31-3.13 (m, 1H), 2.94 (d, J=19.5 Hz, 0.5H), 2.64-2.54 (m, 0.5H), 2.47-2.39 (m, 0.5H), 2.28 (dd, J=7.3, 16.7 Hz, 2H), 2.17-1.88 (m, 1H), 1.80-1.47 (m, 2H), 0.81-0.61 (m, 4H). the precipitate collected washed with 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 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (700 mg, 3.31 mmol) in dry dichloromethane (15 mL) was added 4-bromo-2-chloro-1-isocyanatobenzene (770 mg, 3.31 mmol). The reaction was stirred overnight, diluted with hexane (15 mL), and the precipitate collected and washed with hexane to provide the title compound (1.3 g, 2.93 mmol, 88% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.85 (br. s, 1H), 8.82 (br. s, 1H), 8.50-8.23 (m, 1H), 8.05 (dd, J=5.3, 8.8 Hz, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 3.81 (dd, J=7.6, 9.9 Hz, 0.5H), 3.77-3.39 (m, 2H), 3.31-3.13 (m, 1H), 2.94 (d, J=19.5 Hz, 0.5H), 2.64-2.54 (m, 0.5H), 2.47-2.39 (m, 0.5H), 2.28 (dd, J=7.3, 16.7 Hz, 2H), 2.17-1.88 (m, 1H), 1.80-1.47 (m, 2H), 0.81-0.61 (m, 4H). the precipitate collected washed with hexane

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

実験手順: To a stirred or shaken solution of 157 mg (0.76 mmol) of (4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine (abbreviated as (4S,5S)-amine 1) in pentane (3.5 mL) was added dropwise a solution of 169 mg (0.73 mmol) of 4-bromo-2-chlorophenyl isocyanate in dichloromethane (0.7 mL). A white precipitate was observed after stirring for 0.5 to 2 h. The precipitate was collected, rinsed with pentane, and dried under vacuum to yield 280 mg (88%) of the title compound. In some examples, pentane was used to dissolve the required isocyanate rather than dichloromethane. In addition, if the required isocyanate was a liquid, it was added dropwise as a neat liquid on small-scale reactions such as this. In cases where a precipitate was not observed or the precipitate was not of sufficient purity, the solvent was evaporated, and the residue was purified by column chromatography (hexanes/ethyl acetate) to yield the desired product. after stirring for 0.5 to 2 h The precipitate was collected rinsed with pentane dried under vacuum

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

実験手順: To a solution of 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (700 mg, 3.31 mmol) in dry dichloromethane (15 mL) was added 4-bromo-2-chloro-1-isocyanatobenzene (770 mg, 3.31 mmol). The reaction was stirred overnight, diluted with hexane (15 mL), and the precipitate collected and washed with hexane to provide the title compound (1.3 g, 2.93 mmol, 88% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.85 (br. s, 1H), 8.82 (br. s, 1H), 8.50-8.23 (m, 1H), 8.05 (dd, J=5.3, 8.8 Hz, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 3.81 (dd, J=7.6, 9.9 Hz, 0.5H), 3.77-3.39 (m, 2H), 3.31-3.13 (m, 1H), 2.94 (d, J=19.5 Hz, 0.5H), 2.64-2.54 (m, 0.5H), 2.47-2.39 (m, 0.5H), 2.28 (dd, J=7.3, 16.7 Hz, 2H), 2.17-1.88 (m, 1H), 1.80-1.47 (m, 2H), 0.81-0.61 (m, 4H). the precipitate collected washed with hexane