(1S)-2,3-二氢-1H-印传-1-ol

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to Scheme 7: A mixture of 1-[3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (3b) (0.2 g, 0.771 mmol), tri-n-butylphosphine (0.312 g, 1.54 mmol), 1,1′-(azodicarbonyl)dipiperidine (0.389 g, 1.54 mmol) and (S)-1-indanol in dry toluene (2.5 ml) was stirred at 80° C. for 2 h. Solvents were evaporated in vacuo. The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 81 mg of 1-[(R)-3-(4-fluoro-phenyl)-1-indan-1-yl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (12a) Solvents were evaporated in vacuo The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to Scheme 7: A mixture of 1-[3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (3b) (0.2 g, 0.771 mmol), tri-n-butylphosphine (0.312 g, 1.54 mmol), 1,1′-(azodicarbonyl)dipiperidine (0.389 g, 1.54 mmol) and (S)-1-indanol in dry toluene (2.5 ml) was stirred at 80° C. for 2 h. Solvents were evaporated in vacuo. The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 81 mg of 1-[(R)-3-(4-fluoro-phenyl)-1-indan-1-yl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (12a) Solvents were evaporated in vacuo The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

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

实验步骤: Methanesulfonyl anhydride (3.0 g, 17.2 mmol) as a solution in dichloromethane (8 mL+4 mL) was added to a stirred solution of (S)-1-indanol (1.02 g, 7.6 mmol) and triethylamine (4.4 mL, 31.5 mmol) in dichloromethane (20 mL) at −26° C. (internal, −35° C. external) over 10 minutes. During the addition the internal temperature rose to −20° C. The reaction was maintained at −29° C. (internal, −35° C., external) for 45 minutes before propargylamine (5 mL, 78 mmol) was added over 2 minutes. The reaction was allowed to warm slowly to room temperature overnight before being portioned between ethyl acetate (50 mL) and ice-water (75 mL, pH of solution 9.7). The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL, pH of solution <1). The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL). The combined final organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a brown liquid (0.81 g, 68%). Analysis of this material by chiral GC indicated it to be 46% e.e. During the addition the internal temperature rose to −20° C was added over 2 minutes The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL) were dried (MgSO4) filtered concentrated under reduced pressure

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

实验步骤: Methanesulfonyl anhydride (3.0 g, 17.2 mmol) as a solution in dichloromethane (8 mL+4 mL) was added to a stirred solution of (S)-1-indanol (1.02 g, 7.6 mmol) and triethylamine (4.4 mL, 31.5 mmol) in dichloromethane (20 mL) at −26° C. (internal, −35° C. external) over 10 minutes. During the addition the internal temperature rose to −20° C. The reaction was maintained at −29° C. (internal, −35° C., external) for 45 minutes before propargylamine (5 mL, 78 mmol) was added over 2 minutes. The reaction was allowed to warm slowly to room temperature overnight before being portioned between ethyl acetate (50 mL) and ice-water (75 mL, pH of solution 9.7). The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL, pH of solution <1). The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL). The combined final organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a brown liquid (0.81 g, 68%). Analysis of this material by chiral GC indicated it to be 46% e.e. During the addition the internal temperature rose to −20° C was added over 2 minutes The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL) were dried (MgSO4) filtered concentrated under reduced pressure

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

实验步骤: Methanesulfonyl anhydride (3.0 g, 17.2 mmol) as a solution in dichloromethane (8 mL+4 mL) was added to a stirred solution of (S)-1-indanol (1.02 g, 7.6 mmol) and triethylamine (4.4 mL, 31.5 mmol) in dichloromethane (20 mL) at −26° C. (internal, −35° C. external) over 10 minutes. During the addition the internal temperature rose to −20° C. The reaction was maintained at −29° C. (internal, −35° C., external) for 45 minutes before propargylamine (5 mL, 78 mmol) was added over 2 minutes. The reaction was allowed to warm slowly to room temperature overnight before being portioned between ethyl acetate (50 mL) and ice-water (75 mL, pH of solution 9.7). The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL, pH of solution <1). The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL). The combined final organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a brown liquid (0.81 g, 68%). Analysis of this material by chiral GC indicated it to be 46% e.e. During the addition the internal temperature rose to −20° C was added over 2 minutes The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL) were dried (MgSO4) filtered concentrated under reduced pressure

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to Scheme 7: A mixture of 1-[3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (3b) (0.2 g, 0.771 mmol), tri-n-butylphosphine (0.312 g, 1.54 mmol), 1,1′-(azodicarbonyl)dipiperidine (0.389 g, 1.54 mmol) and (S)-1-indanol in dry toluene (2.5 ml) was stirred at 80° C. for 2 h. Solvents were evaporated in vacuo. The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 81 mg of 1-[(R)-3-(4-fluoro-phenyl)-1-indan-1-yl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (12a) Solvents were evaporated in vacuo The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)