4-苯基-1-氧杂-3-氮杂螺[4.5]癸烷-2-one

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 50 mL dried round bottom flask containing a degassed solution of 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (1 eq., 1.73 mmol) and 4-iodo-N-(quinolin-8-yl)benzamide (1.2 eq.) in DMF (15 mL), potassium carbonate (2.5 eq.) and trans (N,N)-dimethyl cyclohexanediamine (0.5 eq.), was added CuI (0.1 eq). The resulting mixture was then stirred at 120° C. for 15 hours. Reaction progress was monitored by TLC (TLC eluent: 10% MeOH in DCM). The reaction mixture was cooled and poured into crushed ice (5 g). The solid thus obtained was filtered, washed with water (25 mL) and dissolved in DCM. The DCM solution was then washed with water (100 mL), brine (50 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using silica gel and DCM as eluting solvent to yield (R+S) 4-(2-oxo-4-phenyl-1-oxa-3-azaspiro[4.5]decan-3-yl)-N-(quinolin-8-yl)benzamide (90 mg, 11%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.46 (s, 1H), 8.95 (dd, J=4.4, 1.6 Hz, 1H), 8.66 (d, J=6.4 Hz, 1H), 8.44 (dd, J=8.4, 1.6 Hz, 1H), 7.94 (d, J=8.0 Hz, 2H), 7.75-7.72 (m, 3H), 7.68-7.61 (m, 3H), 7.32-7.39 (m, 4H), 5.52 (s, 1H), 2.08-2.11 (m, 1H), 1.83-1.89 (m, 1H), 1.74-1.53 (m, 3H), 1.35-1.42 (m, 2H), 1.20-1.23 (m, 3H). m/z (ESI) 478.2 (M+H)+. To a 50 mL dried round bottom flask Reaction progress The reaction mixture was cooled poured The solid thus obtained was filtered washed with water (25 mL) dissolved in DCM The DCM solution was then washed with water (100 mL), brine (50 mL) dried over anhydrous Na2SO4 filtered concentrated purified by column chromatography as eluting solvent

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 100 mL round bottom flask charged with 2-(1-hydroxycyclohexyl)-2-phenylacetic acid (6.5 g, 28.14 mmole, 1 eq.) in toluene (100 mL) were added TEA (2.5 eq) and diphenyl phosphoryl azide (2 eq). The resulting mixture was then stirred at 120° C. for 12 hours. Reaction progress was monitored by TLC (TLC eluent: 30% EtOAc in hexane). The reaction mixture was then cooled and toluene was removed under reduced pressure to afford the product. The product thus obtained was purified by column chromatography using silica gel and eluting with 10% EtOAc in hexane to afford 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (2 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ: 8.04 (s, 1H), 7.26-7.41 (m, 5H), 4.54 (s, 1H), 1.93-1.97 (m, 1H), 1.48-1.78 (m, 4H), 1.12-1.33 (m, 5H). m/z (ESI) 232.1 (M+H)+. Reaction progress The reaction mixture was then cooled toluene was removed under reduced pressure to afford the product The product thus obtained was purified by column chromatography eluting with 10% EtOAc in hexane

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 100 mL round bottom flask charged with 2-(1-hydroxycyclohexyl)-2-phenylacetic acid (6.5 g, 28.14 mmole, 1 eq.) in toluene (100 mL) were added TEA (2.5 eq) and diphenyl phosphoryl azide (2 eq). The resulting mixture was then stirred at 120° C. for 12 hours. Reaction progress was monitored by TLC (TLC eluent: 30% EtOAc in hexane). The reaction mixture was then cooled and toluene was removed under reduced pressure to afford the product. The product thus obtained was purified by column chromatography using silica gel and eluting with 10% EtOAc in hexane to afford 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (2 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ: 8.04 (s, 1H), 7.26-7.41 (m, 5H), 4.54 (s, 1H), 1.93-1.97 (m, 1H), 1.48-1.78 (m, 4H), 1.12-1.33 (m, 5H). m/z (ESI) 232.1 (M+H)+. Reaction progress The reaction mixture was then cooled toluene was removed under reduced pressure to afford the product The product thus obtained was purified by column chromatography eluting with 10% EtOAc in hexane

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 50 mL dried round bottom flask containing a degassed solution of 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (1 eq., 1.73 mmol) and 4-iodo-N-(quinolin-8-yl)benzamide (1.2 eq.) in DMF (15 mL), potassium carbonate (2.5 eq.) and trans (N,N)-dimethyl cyclohexanediamine (0.5 eq.), was added CuI (0.1 eq). The resulting mixture was then stirred at 120° C. for 15 hours. Reaction progress was monitored by TLC (TLC eluent: 10% MeOH in DCM). The reaction mixture was cooled and poured into crushed ice (5 g). The solid thus obtained was filtered, washed with water (25 mL) and dissolved in DCM. The DCM solution was then washed with water (100 mL), brine (50 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using silica gel and DCM as eluting solvent to yield (R+S) 4-(2-oxo-4-phenyl-1-oxa-3-azaspiro[4.5]decan-3-yl)-N-(quinolin-8-yl)benzamide (90 mg, 11%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.46 (s, 1H), 8.95 (dd, J=4.4, 1.6 Hz, 1H), 8.66 (d, J=6.4 Hz, 1H), 8.44 (dd, J=8.4, 1.6 Hz, 1H), 7.94 (d, J=8.0 Hz, 2H), 7.75-7.72 (m, 3H), 7.68-7.61 (m, 3H), 7.32-7.39 (m, 4H), 5.52 (s, 1H), 2.08-2.11 (m, 1H), 1.83-1.89 (m, 1H), 1.74-1.53 (m, 3H), 1.35-1.42 (m, 2H), 1.20-1.23 (m, 3H). m/z (ESI) 478.2 (M+H)+. To a 50 mL dried round bottom flask Reaction progress The reaction mixture was cooled poured The solid thus obtained was filtered washed with water (25 mL) dissolved in DCM The DCM solution was then washed with water (100 mL), brine (50 mL) dried over anhydrous Na2SO4 filtered concentrated purified by column chromatography as eluting solvent

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 100 mL round bottom flask charged with 2-(1-hydroxycyclohexyl)-2-phenylacetic acid (6.5 g, 28.14 mmole, 1 eq.) in toluene (100 mL) were added TEA (2.5 eq) and diphenyl phosphoryl azide (2 eq). The resulting mixture was then stirred at 120° C. for 12 hours. Reaction progress was monitored by TLC (TLC eluent: 30% EtOAc in hexane). The reaction mixture was then cooled and toluene was removed under reduced pressure to afford the product. The product thus obtained was purified by column chromatography using silica gel and eluting with 10% EtOAc in hexane to afford 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (2 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ: 8.04 (s, 1H), 7.26-7.41 (m, 5H), 4.54 (s, 1H), 1.93-1.97 (m, 1H), 1.48-1.78 (m, 4H), 1.12-1.33 (m, 5H). m/z (ESI) 232.1 (M+H)+. Reaction progress The reaction mixture was then cooled toluene was removed under reduced pressure to afford the product The product thus obtained was purified by column chromatography eluting with 10% EtOAc in hexane