二草氨酸乙酯乙酯

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.000 g of compound (14) as obtained from example 8 (3.595 mmol) in 40 mL ethanol were added at room temperature 2.215 g cerium (III) chloride (grinded, 8.99 mmol, 2.5 eq). The suspension was placed in an ultrasonic bath for 10 min and was then cooled to 15° C. by a water bath. 2.40 g sodium borohydride (61.1 mmol, 17 eq) were added in 6 portions over 3 h. After additional 2 h at room temperature, the suspension was poured onto 800 mL saturated aqueous sodium hydrogencarbonate/brine (1:1) and the mixture was vigorously stirred for 13 h prior to extraction with five times 400 mL, dichloromethane/ethanol (4:1). The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar). The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1) yielding the title compound (623.2 mg, 2.21 mmol, 61% by weight) as a white solid. After additional 2 h at room temperature to extraction with five times 400 mL, dichloromethane/ethanol (4:1) The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar) The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred (-78° C.) solution of sec-butyllithium (1.3M in cyclohexane; 6.6 ml) and TMEDA (1.3 ml) in anhydrous ether (4.0 ml) was added via canula under a N2 atmosphere a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (1.69 g), in anhydrous ether (4.0 ml). The solution was stirred at -78° C. for 2.5 hours and then added via canula, under N2, to a stirred (-78° C.) solution of N,N-diethylamino-oxo-acetic acid, ethyl ester (3.6 g) in diethyl ether (8.0 ml). The solution was stirred at -78° C. for 3 hours and gradually allowed to warm to room temperature over 2 hours. The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl. The organic phase was separated and washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine, and dried (Na2SO 4). The crude residue was purified using preparative HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane). The appropriate fractions were combined and concentrated to a foam which solidified upon trituration with hexane, to afford 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diethyl amide. added via canula, under N2 The solution was stirred at -78° C. for 3 hours to warm to room temperature over 2 hours The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl The organic phase was separated washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine dried (Na2SO 4) The crude residue was purified HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane) concentrated to a foam which

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred (-78° C.) solution of sec-butyllithium (1.3M in cyclohexane; 6.6 ml) and TMEDA (1.3 ml) in anhydrous ether (4.0 ml) was added via canula under a N2 atmosphere a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (1.69 g), in anhydrous ether (4.0 ml). The solution was stirred at -78° C. for 2.5 hours and then added via canula, under N2, to a stirred (-78° C.) solution of N,N-diethylamino-oxo-acetic acid, ethyl ester (3.6 g) in diethyl ether (8.0 ml). The solution was stirred at -78° C. for 3 hours and gradually allowed to warm to room temperature over 2 hours. The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl. The organic phase was separated and washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine, and dried (Na2SO 4). The crude residue was purified using preparative HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane). The appropriate fractions were combined and concentrated to a foam which solidified upon trituration with hexane, to afford 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diethyl amide. added via canula, under N2 The solution was stirred at -78° C. for 3 hours to warm to room temperature over 2 hours The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl The organic phase was separated washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine dried (Na2SO 4) The crude residue was purified HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane) concentrated to a foam which

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred (-78° C.) solution of sec-butyllithium (1.3M in cyclohexane; 6.6 ml) and TMEDA (1.3 ml) in anhydrous ether (4.0 ml) was added via canula under a N2 atmosphere a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (1.69 g), in anhydrous ether (4.0 ml). The solution was stirred at -78° C. for 2.5 hours and then added via canula, under N2, to a stirred (-78° C.) solution of N,N-diethylamino-oxo-acetic acid, ethyl ester (3.6 g) in diethyl ether (8.0 ml). The solution was stirred at -78° C. for 3 hours and gradually allowed to warm to room temperature over 2 hours. The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl. The organic phase was separated and washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine, and dried (Na2SO 4). The crude residue was purified using preparative HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane). The appropriate fractions were combined and concentrated to a foam which solidified upon trituration with hexane, to afford 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diethyl amide. added via canula, under N2 The solution was stirred at -78° C. for 3 hours to warm to room temperature over 2 hours The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl The organic phase was separated washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine dried (Na2SO 4) The crude residue was purified HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane) concentrated to a foam which

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.000 g of compound (14) as obtained from example 8 (3.595 mmol) in 40 mL ethanol were added at room temperature 2.215 g cerium (III) chloride (grinded, 8.99 mmol, 2.5 eq). The suspension was placed in an ultrasonic bath for 10 min and was then cooled to 15° C. by a water bath. 2.40 g sodium borohydride (61.1 mmol, 17 eq) were added in 6 portions over 3 h. After additional 2 h at room temperature, the suspension was poured onto 800 mL saturated aqueous sodium hydrogencarbonate/brine (1:1) and the mixture was vigorously stirred for 13 h prior to extraction with five times 400 mL, dichloromethane/ethanol (4:1). The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar). The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1) yielding the title compound (623.2 mg, 2.21 mmol, 61% by weight) as a white solid. After additional 2 h at room temperature to extraction with five times 400 mL, dichloromethane/ethanol (4:1) The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar) The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: mL ethyl magnesium bromide solution (191.8 mmol, 1.10 eq) were diluted with 182.6 mL diethylether. The solution was cooled to −15° C. and a solution of 30.20 g of compound (8) as obtained from example 1 (174.4 mmol) in 60.4 mL diethylether was added dropwise. The resulting viscous suspension was stirred for additional 75 min at −15° C. Subsequently, the reaction was quenched by addition of 14.96 mL acetic acid (261.6 mmol, 1.5 eq). Then, 35 mL water were added to dissolve all salts and the cooling bath was removed. After 15 min, the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate and was filtered. The filter cake was washed with 40 mL diethylether. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 86° C. at 2.5 mbar) furnishing the title compound (18.66 g, 118.7 mmol, 68% by weight) as colorless liquid. was added dropwise to dissolve all salts the cooling bath was removed After 15 min the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate was filtered The filter cake was washed with 40 mL diethylether After evaporation of solvent in a rotary evaporator (40° C./10 mbar) the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid Purification a high vacuum distillation (bp 86° C. at 2.5 mbar)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 30.00 g (203.2 mmol) diethyloxalate (7) were added at room temperature 42.2 mL diethylamine (406.4 mmol, 2.0 eq). The colorless clear solution was heated to reflux (oil bath temperature: 90° C.) and the reaction was monitored by HPLC. After 2.5 h, the resulting yellow-orange liquid was cooled to room temperature and all volatile compounds (ethanol, diethylamine) were removed in a rotary evaporator (50° C., 10 mbar) furnishing the crude product (35.073 g, 100% by weight) as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 85° C. at 0.08 mbar) furnishing the title compound (30.22 g, 174.4 mmol, 86% by weight) as colorless liquid. The colorless clear solution was heated the resulting yellow-orange liquid was cooled to room temperature all volatile compounds (ethanol, diethylamine) were removed in a rotary evaporator (50° C., 10 mbar) furnishing the crude product (35.073 g, 100% by weight) as a yellow liquid Purification a high vacuum distillation (bp 85° C. at 0.08 mbar)

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.000 g of compound (14) as obtained from example 8 (3.595 mmol) in 40 mL ethanol were added at room temperature 2.215 g cerium (III) chloride (grinded, 8.99 mmol, 2.5 eq). The suspension was placed in an ultrasonic bath for 10 min and was then cooled to 15° C. by a water bath. 2.40 g sodium borohydride (61.1 mmol, 17 eq) were added in 6 portions over 3 h. After additional 2 h at room temperature, the suspension was poured onto 800 mL saturated aqueous sodium hydrogencarbonate/brine (1:1) and the mixture was vigorously stirred for 13 h prior to extraction with five times 400 mL, dichloromethane/ethanol (4:1). The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar). The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1) yielding the title compound (623.2 mg, 2.21 mmol, 61% by weight) as a white solid. After additional 2 h at room temperature to extraction with five times 400 mL, dichloromethane/ethanol (4:1) The combined organic extracts were evaporated in a rotary evaporator (50° C., 5 mbar) The crude product was obtained as a purple-red solid (879.6 mg, 87% by weight), which was purified by trituration with 5.25 mL dichloromethane/methyl tert-butyl ether (2:1)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: mL ethyl magnesium bromide solution (191.8 mmol, 1.10 eq) were diluted with 182.6 mL diethylether. The solution was cooled to −15° C. and a solution of 30.20 g of compound (8) as obtained from example 1 (174.4 mmol) in 60.4 mL diethylether was added dropwise. The resulting viscous suspension was stirred for additional 75 min at −15° C. Subsequently, the reaction was quenched by addition of 14.96 mL acetic acid (261.6 mmol, 1.5 eq). Then, 35 mL water were added to dissolve all salts and the cooling bath was removed. After 15 min, the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate and was filtered. The filter cake was washed with 40 mL diethylether. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 86° C. at 2.5 mbar) furnishing the title compound (18.66 g, 118.7 mmol, 68% by weight) as colorless liquid. was added dropwise to dissolve all salts the cooling bath was removed After 15 min the mixture was washed twice with 200 mL, pH-7-buffer and the organic phase was dried over 20 g sodium sulfate was filtered The filter cake was washed with 40 mL diethylether After evaporation of solvent in a rotary evaporator (40° C./10 mbar) the crude product (26.33 g, 96% by weight) was obtained as a yellow liquid Purification a high vacuum distillation (bp 86° C. at 2.5 mbar)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 30.00 g (203.2 mmol) diethyloxalate (7) were added at room temperature 42.2 mL diethylamine (406.4 mmol, 2.0 eq). The colorless clear solution was heated to reflux (oil bath temperature: 90° C.) and the reaction was monitored by HPLC. After 2.5 h, the resulting yellow-orange liquid was cooled to room temperature and all volatile compounds (ethanol, diethylamine) were removed in a rotary evaporator (50° C., 10 mbar) furnishing the crude product (35.073 g, 100% by weight) as a yellow liquid. Purification was achieved using a high vacuum distillation (bp 85° C. at 0.08 mbar) furnishing the title compound (30.22 g, 174.4 mmol, 86% by weight) as colorless liquid. The colorless clear solution was heated the resulting yellow-orange liquid was cooled to room temperature all volatile compounds (ethanol, diethylamine) were removed in a rotary evaporator (50° C., 10 mbar) furnishing the crude product (35.073 g, 100% by weight) as a yellow liquid Purification a high vacuum distillation (bp 85° C. at 0.08 mbar)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred (-78° C.) solution of sec-butyllithium (1.3M in cyclohexane; 6.6 ml) and TMEDA (1.3 ml) in anhydrous ether (4.0 ml) was added via canula under a N2 atmosphere a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (1.69 g), in anhydrous ether (4.0 ml). The solution was stirred at -78° C. for 2.5 hours and then added via canula, under N2, to a stirred (-78° C.) solution of N,N-diethylamino-oxo-acetic acid, ethyl ester (3.6 g) in diethyl ether (8.0 ml). The solution was stirred at -78° C. for 3 hours and gradually allowed to warm to room temperature over 2 hours. The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl. The organic phase was separated and washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine, and dried (Na2SO 4). The crude residue was purified using preparative HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane). The appropriate fractions were combined and concentrated to a foam which solidied upon trituration with hexane, to afford 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diethyl amide. added via canula, under N2 The solution was stirred at -78° C. for 3 hours to warm to room temperature over 2 hours The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl The organic phase was separated washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine dried (Na2SO 4) The crude residue was purified HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane) concentrated to a foam which

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred (-78° C.) solution of sec-butyllithium (1.3M in cyclohexane; 6.6 ml) and TMEDA (1.3 ml) in anhydrous ether (4.0 ml) was added via canula under a N2 atmosphere a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (1.69 g), in anhydrous ether (4.0 ml). The solution was stirred at -78° C. for 2.5 hours and then added via canula, under N2, to a stirred (-78° C.) solution of N,N-diethylamino-oxo-acetic acid, ethyl ester (3.6 g) in diethyl ether (8.0 ml). The solution was stirred at -78° C. for 3 hours and gradually allowed to warm to room temperature over 2 hours. The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl. The organic phase was separated and washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine, and dried (Na2SO 4). The crude residue was purified using preparative HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane). The appropriate fractions were combined and concentrated to a foam which solidified upon trituration with hexane, to afford 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diethyl amide. added via canula, under N2 The solution was stirred at -78° C. for 3 hours to warm to room temperature over 2 hours The mixture was quenched by the addition of an aqueous solution of saturated NH4Cl The organic phase was separated washed with two 50 ml portions of an aqueous solution of saturated NaHCO3, with brine dried (Na2SO 4) The crude residue was purified HPLC (silica gel, loading and eluting with 3% methanol in dichloromethane) concentrated to a foam which