tert-butyl 1,8-diazaspiro[4.5]decane-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

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 solution of stirring terephthaloyl chloride (338 mg, 1.664 mmol) in 20 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (473 mg, 1.664 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (400 mg, 1.664 mmol) was then added, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (1.72 g, 4.992 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 20 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (4 mL) and stirred to form suspension, then treated with trifluoroacetic acid (4 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (4 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (1 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (1 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: Prepared according to the method used in the preparation of [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-cyclopropylmethyl-amine using 1,8-diaza-spiro[4.5]decane-1-carboxylic acid tert-butyl ester in place of cyclopropanemethylamine. The title compound was obtained as a white solid (184 mg, 45%). Prepared

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

実験手順: To a solution of stirring terephthaloyl chloride (338 mg, 1.664 mmol) in 20 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (473 mg, 1.664 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (400 mg, 1.664 mmol) was then added, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (1.72 g, 4.992 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 20 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (4 mL) and stirred to form suspension, then treated with trifluoroacetic acid (4 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (4 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (1 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (338 mg, 1.664 mmol) in 20 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (473 mg, 1.664 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (400 mg, 1.664 mmol) was then added, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (1.72 g, 4.992 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 20 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (4 mL) and stirred to form suspension, then treated with trifluoroacetic acid (4 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (4 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (1 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (338 mg, 1.664 mmol) in 20 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (473 mg, 1.664 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (400 mg, 1.664 mmol) was then added, followed by the addition of diisopropylethylamine (290 μL, 1.664 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (1.72 g, 4.992 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 20 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (4 mL) and stirred to form suspension, then treated with trifluoroacetic acid (4 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (4 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-70-95% acetonitrile/water with 0.1% formic acid)

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

実験手順: To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1. to stir for 1 hour at room temperature stirred overnight at room temperature The mixture was then fully dissolved filtered concentrated Added dichloromethane (1 mL) and stirred to form suspension The reaction mixture was concentrated after 2 hours of stirring at room temperature the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)