5-Boc-八氢吡咯并[3,4-c]吡啶

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product from Example 68A (40 mg, 0.16 mmol) was mixed with tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (55 mg, 0.24 mmol) and to this was added 2-methoxyethanol (0.65 mL), and N,N-diisopropylethylamine (0.20 mL, 1.2 mmol); the reaction was heated at 115° C. for 16 hours, cooled, diluted with CH2Cl2 (25 mL) and washed with 1 M NaOH (10 mL). The aqueous layer was extracted with CH2Cl2 (15 mL). The combined organics were dried (MgSO4), filtered, concentrated and chromatographed and eluted with a gradient of 1:0 to 0:1 CH2Cl2:EtOAc to provide the title compound. cooled washed with 1 M NaOH (10 mL) The aqueous layer was extracted with CH2Cl2 (15 mL) The combined organics were dried (MgSO4) filtered concentrated chromatographed eluted with a gradient of 1:0 to 0:1 CH2Cl2

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product from Example 68A (40 mg, 0.16 mmol) was mixed with tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (55 mg, 0.24 mmol) and to this was added 2-methoxyethanol (0.65 mL), and N,N-diisopropylethylamine (0.20 mL, 1.2 mmol); the reaction was heated at 115° C. for 16 hours, cooled, diluted with CH2Cl2 (25 mL) and washed with 1 M NaOH (10 mL). The aqueous layer was extracted with CH2Cl2 (15 mL). The combined organics were dried (MgSO4), filtered, concentrated and chromatographed and eluted with a gradient of 1:0 to 0:1 CH2Cl2:EtOAc to provide the title compound. cooled washed with 1 M NaOH (10 mL) The aqueous layer was extracted with CH2Cl2 (15 mL) The combined organics were dried (MgSO4) filtered concentrated chromatographed eluted with a gradient of 1:0 to 0:1 CH2Cl2

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

实验步骤: 2-Benzyloctahydropyrrolo[3,4-c]pyridine-5-carboxylic acid tert-butyl ester (Example A26, 24.98 g, 78.8 mmol) in 400 mL of methanol is treated with 2.5 g of 20% Pd/C and shaken for 20.5 hours under 50 PSI of hydrogen. The solution is filtered and concentrated to afford 17.8 g of the title compound as a solid. MS APCI: m/z 228 (MH+). The solution is filtered concentrated

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

实验步骤: A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (1.70 g), 1-bromo-3-chloropropane (1.70 mL) and K2CO3 (3.30 g) in acetone was heated to reflux for 10 h, then cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH) to give the title compound as yellow oil (0.79 g, 35.00%), HPLC: 80.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 10 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH)

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

实验步骤: A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (1.70 g), 1-bromo-3-chloropropane (1.70 mL) and K2CO3 (3.30 g) in acetone was heated to reflux for 10 h, then cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH) to give the title compound as yellow oil (0.79 g, 35.00%), HPLC: 80.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 10 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH)

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

实验步骤: To a solution of tert-butyl 2-benzylhexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (1.60 g) in EtOAc was added a catalytic amount of 20% Pd(OH)2/C. The suspension was stirred for 3 h at room temperature under H2 and filtered. The filtrate was concentrated in vacuo to give the title compound as colorless oil (0.68 g, 60%). The crude product was used for the next step without further purification. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 227.4 (M+1). filtered The filtrate was concentrated in vacuo

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

实验步骤: 2-Benzyloctahydropyrrolo[3,4-c]pyridine-5-carboxylic acid tert-butyl ester (Example A26, 24.98 g, 78.8 mmol) in 400 mL of methanol is treated with 2.5 g of 20% Pd/C and shaken for 20.5 hours under 50 PSI of hydrogen. The solution is filtered and concentrated to afford 17.8 g of the title compound as a solid. MS APCI: m/z 228 (MH+). The solution is filtered concentrated

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

实验步骤: 2-Benzyloctahydropyrrolo[3,4-c]pyridine-5-carboxylic acid tert-butyl ester (Example A26, 24.98 g, 78.8 mmol) in 400 mL of methanol is treated with 2.5 g of 20% Pd/C and shaken for 20.5 hours under 50 PSI of hydrogen. The solution is filtered and concentrated to afford 17.8 g of the title compound as a solid. MS APCI: m/z 228 (MH+). The solution is filtered concentrated

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

实验步骤: The title compound was prepared by analogy to the procedure of Example 1.3, except using tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate and 8-iodo-3-(3-(trifluoromethoxy)phenylsulfonyl)quinoline. 130 mg (54%) of the title compound were obtained as a pale yellow solid. The title compound was prepared by analogy to the procedure of Example 1.3

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

实验步骤: The title compound was prepared by analogy to the procedure of Example 1.3, except using tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate and 3-(4-fluorophenylsulfonyl)-8-iodoquinoline. 130 mg (55%) of the title compound were obtained as a pale yellow oil. The title compound was prepared by analogy to the procedure of Example 1.3

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

实验步骤: The title compound was prepared by analogy to the procedure of Example 1.3, except using tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate and 8-iodo-3-(3-(trifluoromethoxy)phenylsulfonyl)quinoline. 130 mg (54%) of the title compound were obtained as a pale yellow solid. The title compound was prepared by analogy to the procedure of Example 1.3

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

实验步骤: The title compound was prepared by analogy to the procedure of Example 1.3, except using tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate and 3-(4-fluorophenylsulfonyl)-8-iodoquinoline. 130 mg (55%) of the title compound were obtained as a pale yellow oil. The title compound was prepared by analogy to the procedure of Example 1.3