4-(羟甲基)-1,4-二甲基咪唑啉-2-one

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

实验步骤: A solution of 4-(hydroxymethyl)-1,4-dimethylimidazolidin-2-one (3.3 g, 22.7 mmol), anhydrous pyridine (8.25 ml, 102 mmol), and thionyl chloride (8.26 ml, 114 mmol) in 46 ml of 1,2-dichloroethane was heated at reflux temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane, and filtered to remove solids. The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane, and the combined organic fractions were dried over sodium sulfate and concentrated to 2.2 g of yellow oil. The crude product was purified by column chromatorgraphy, eluting from silica gel with a gradient of 0-10% methanol in dichloromethane to give 897 mg of desired product as a white solid (25% yield). 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 2.79 (s, 3H), 3.17-3.20 (d, J=9.2 Hz, 1H), 3.36-3.39 (d, J=9.2 Hz, 1H), 3.50 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 24.2, 30.3, 51.5, 55.0, 57.0, 160.6. LRMS (ESI/APCI): 163 [M+H]+. at reflux temperature for 8 hours The reaction mixture was concentrated under reduced pressure diluted with dichloromethane filtered to remove solids The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane the combined organic fractions were dried over sodium sulfate concentrated to 2.2 g of yellow oil The crude product was purified by column chromatorgraphy eluting from silica gel with a gradient of 0-10% methanol in dichloromethane

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

实验步骤: A solution of 4-(hydroxymethyl)-1,4-dimethylimidazolidin-2-one (3.3 g, 22.7 mmol), anhydrous pyridine (8.25 ml, 102 mmol), and thionyl chloride (8.26 ml, 114 mmol) in 46 ml of 1,2-dichloroethane was heated at reflux temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane, and filtered to remove solids. The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane, and the combined organic fractions were dried over sodium sulfate and concentrated to 2.2 g of yellow oil. The crude product was purified by column chromatorgraphy, eluting from silica gel with a gradient of 0-10% methanol in dichloromethane to give 897 mg of desired product as a white solid (25% yield). 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 2.79 (s, 3H), 3.17-3.20 (d, J=9.2 Hz, 1H), 3.36-3.39 (d, J=9.2 Hz, 1H), 3.50 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 24.2, 30.3, 51.5, 55.0, 57.0, 160.6. LRMS (ESI/APCI): 163 [M+H]+. at reflux temperature for 8 hours The reaction mixture was concentrated under reduced pressure diluted with dichloromethane filtered to remove solids The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane the combined organic fractions were dried over sodium sulfate concentrated to 2.2 g of yellow oil The crude product was purified by column chromatorgraphy eluting from silica gel with a gradient of 0-10% methanol in dichloromethane

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

实验步骤: In a round bottom flask, a mixture of 2-amino-2-methyl-3-(methylamino)propan-1-ol hydrochloride (3.3 g, 21 mmol) and urea (1.26 g, 21 mmol) were heated in a 200° C. sand bath for 1 hour until ammonia gas ceased to evolve. The resultant mixture was suspended in dichloromethane and filtered to remove insoluble material. The organic solution was concentrated to 3.3 g of black solid and purified by column chromatography, eluting from silica gel with a gradient of 1-12% methanol in dichloromethane to give 1.3 g of desired product as a tan oil (45% yield). 1H NMR (400 MHz, CDCl3) δ1.26 (s, 3H), 2.76 (s, 3H), 3.07-3.9 (d, J=8.8 Hz, 1H), 3.36-3.36 (d, J=8.8 Hz, 1H), 3.43-3.44 (d, J=2.1 Hz, 2H), 3.46 (s, 1H). 13C NMR (100 MHz, CDCl3/MeOD) δ 23.5, 30.1, 50.0, 55.7, 67.7, 161.9. LRMS (ESI/APCI): 145 [M+H]+. filtered to remove insoluble material The organic solution was concentrated to 3.3 g of black solid purified by column chromatography eluting from silica gel with a gradient of 1-12% methanol in dichloromethane

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

实验步骤: A solution of 4-(hydroxymethyl)-1,4-dimethylimidazolidin-2-one (250 mg, 1.72 mmol) in methanol (2.5 ml) was cooled to 0° C. tert-Butylhypochlorite (236 ul, 2.1 mmol) was added. The resulting solution was stirred for 30 minutes, then concentrated under reduced pressure to a crude residue. The crude material was purified by column chromatography (1 to 12% methanol in dichloromethane) to give the desired product as a white solid (168 mg, 0.941 mmol, 54%). 1H NMR (400 MHz, D2O) δ 1.16 (s, 3H), 2.74 (s, 3H), 3.25-3.27 (d, J=9.2 Hz, 1H), 3.38-3.41 (d, J=12.6 Hz, 1H), 3.47-3.49 (d, J=9.2 Hz, 2H), 3.64-3.67 (d, J=12.6 Hz, 1H). 13C NMR (100 MHz, D2O) δ 18.1, 30.8, 53.2, 62.8, 64.5, 161.6. LRMS (ESI/APCI) m/z 179 [M+H]+. was added concentrated under reduced pressure to a crude residue The crude material was purified by column chromatography (1 to 12% methanol in dichloromethane)

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

实验步骤: In a round bottom flask, a mixture of 2-amino-2-methyl-3-(methylamino)propan-1-ol hydrochloride (3.3 g, 21 mmol) and urea (1.26 g, 21 mmol) were heated in a 200° C. sand bath for 1 hour until ammonia gas ceased to evolve. The resultant mixture was suspended in dichloromethane and filtered to remove insoluble material. The organic solution was concentrated to a black solid and purified by purified by column chromatography (1 to 12% methanol in dichloromethane) to give the desired product as a tan oil (1.3 g, 9.0 mmol, 45% yield). 1H NMR (400 MHz, CDCl3) δ 1.26 (s, 3H), 2.76 (s, 3H), 3.07-3.9 (d, J=8.8 Hz, 1H), 3.36-3.36 (d, J=8.8 Hz, 1H), 3.43-3.44 (d, J=2.1 Hz, 2H), 3.46 (s, 1H). 13C NMR (100 MHz, CDCl3/MeOD) δ 23.5, 30.1, 50.0, 55.7, 67.7, 161.9. LRMS (ESI/APCI) m/z 145 [M+H]+. filtered to remove insoluble material The organic solution was concentrated to a black solid purified by purified by column chromatography (1 to 12% methanol in dichloromethane)

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

实验步骤: A solution of 4-(hydroxymethyl)-1,4-dimethylimidazolidin-2-one (3.3 g, 22.7 mmol), anhydrous pyridine (8.25 ml, 102 mmol), and thionyl chloride (8.26 ml, 114 mmol) in 46 ml of 1,2-dichloroethane was heated at reflux temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane, and filtered to remove solids. The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane, and the combined organic fractions were dried over sodium sulfate and concentrated to 2.2 g of yellow oil. The crude product was purified by column chromatorgraphy, eluting from silica gel with a gradient of 0-10% methanol in dichloromethane to give 897 mg of desired product as a white solid (25% yield). 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 2.79 (s, 3H), 3.17-3.20 (d, J=9.2 Hz, 1H), 3.36-3.39 (d, J=9.2 Hz, 1H), 3.50 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 24.2, 30.3, 51.5, 55.0, 57.0, 160.6. LRMS (ESI/APCI): 163 [M+H]+. at reflux temperature for 8 hours The reaction mixture was concentrated under reduced pressure diluted with dichloromethane filtered to remove solids The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane the combined organic fractions were dried over sodium sulfate concentrated to 2.2 g of yellow oil The crude product was purified by column chromatorgraphy eluting from silica gel with a gradient of 0-10% methanol in dichloromethane

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

实验步骤: In a round bottom flask, a mixture of 2-amino-2-methyl-3-(methylamino)propan-1-ol hydrochloride (3.3 g, 21 mmol) and urea (1.26 g, 21 mmol) were heated in a 200° C. sand bath for 1 hour until ammonia gas ceased to evolve. The resultant mixture was suspended in dichloromethane and filtered to remove insoluble material. The organic solution was concentrated to 3.3 g of black solid and purified by column chromatography, eluting from silica gel with a gradient of 1-12% methanol in dichloromethane to give 1.3 g of desired product as a tan oil (45% yield). 1H NMR (400 MHz, CDCl3) δ1.26 (s, 3H), 2.76 (s, 3H), 3.07-3.9 (d, J=8.8 Hz, 1H), 3.36-3.36 (d, J=8.8 Hz, 1H), 3.43-3.44 (d, J=2.1 Hz, 2H), 3.46 (s, 1H). 13C NMR (100 MHz, CDCl3/MeOD) δ 23.5, 30.1, 50.0, 55.7, 67.7, 161.9. LRMS (ESI/APCI): 145 [M+H]+. filtered to remove insoluble material The organic solution was concentrated to 3.3 g of black solid purified by column chromatography eluting from silica gel with a gradient of 1-12% methanol in dichloromethane