4-(2-BOC-氨乙基)哌啶

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

实验步骤: 0.5 g of 4-(2-tert-butoxycarbonylaminoethyl)-piperidine and 0.61 ml of triethylamine are dissolved in 5 ml of dichloromethane and, at 0° C., 0.22 ml of acetyl chloride is added. The reaction mixture is stirred at room temperature for 7 hours and then washed with water. The organic phase is concentrated by evaporation and purified by FC (10 g of silica gel, ethyl acetate/methanol=9:1). The title compound is obtained: Rf (ethyl acetate/methanol=9:1)=0.39. washed with water The organic phase is concentrated by evaporation purified by FC (10 g of silica gel, ethyl acetate/methanol=9:1)

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

实验步骤: 0.5 g of 4-(2-tert-butoxycarbonylaminoethyl)-piperidine and 0.61 ml of triethylamine are dissolved in 5 ml of dichloromethane and, at 0° C., 0.22 ml of acetyl chloride is added. The reaction mixture is stirred at room temperature for 7 hours and then washed with water. The organic phase is concentrated by evaporation and purified by FC (10 g of silica gel, ethyl acetate/methanol=9:1). The title compound is obtained: Rf (ethyl acetate/methanol=9:1)=0.39. washed with water The organic phase is concentrated by evaporation purified by FC (10 g of silica gel, ethyl acetate/methanol=9:1)

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

实验步骤: Following the procedure of Example 9(e) 3-(4-cyano phenoxy)-5-hydroxy benzoic acid 1.6 g (6.3 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (1.43 g, 6.27 mmol) were used to afford 2.0 g of the required product. Percentage purity (LCMS): 79.6%, (M+1)=465.2+1.

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

实验步骤: 2,4-Dihydroxy benzoic acid (1.25 g, 8.11 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (1.85 g, 8.11 mmol) and other reagents as described in Example 9(e) were used to afford 1.13 g of the required product. 1H NMR (DMSO-d6): δ 1.05 (2H, m), 1.25 (2H, m), 1.4 (9H, s), 1.65 (2H, m), 2.75 (2H, m), 2.95 (2H, m), 3.15 (1H, m), 4.0 (2H, m), 6.24 (2H, m), 6.78 (1H, m), 6.9 (1H, d), 9.6 (2H, brs).

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

实验步骤: Following the procedure of Example 5(c) 3-(4-cyano-benzyloxy)-5-(4-cyano-phenoxy)-benzoic acid 0.8 g (2.16 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.49 g, 2.16 mmol) were used to afford 0.92 g of the required product. 1H NMR (DMSO-d6): δ 1.10 (2H, m), 1.30 (2H, m), 1.4 (9H, s), 1.50 (2H, m), 1.75 (1H, m), 2.70 (1H, m), 2.8 (3H, m), 3.5 (1H, m), 4.4 (1H, m), 5.2 (2H, s), 6.65 (1H, s), 6.78 (1H, m), 6.88 (2H, m), 7.16 (2H, s), 7.64 (2H, d), 7.88 (4H, m).

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

实验步骤: Following the procedure of Example 5(c) 3-(4-cyano-benzyloxy)-5-(4-cyano-phenoxy)-benzoic acid 0.8 g (2.16 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.49 g, 2.16 mmol) were used to afford 0.92 g of the required product. 1H NMR (DMSO-d6): δ 1.10 (2H, m), 1.30 (2H, m), 1.4 (9H, s), 1.50 (2H, m), 1.75 (1H, m), 2.70 (1H, m), 2.8 (3H, m), 3.5 (1H, m), 4.4 (1H, m), 5.2 (2H, s), 6.65 (1H, s), 6.78 (1H, m), 6.88 (2H, m), 7.16 (2H, s), 7.64 (2H, d), 7.88 (4H, m).

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

实验步骤: Following the procedure of Example 5(c) 3-(3-cyano-benzyloxy)-5-(4-cyano-phenoxy)-benzoic acid 0.75 g (2.02 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.46 g, 2.02 mmol) were used to afford 0.7 g of the required product. Percentage purity (LCMS): 62.3%, (M+1)=480.2+1 (de-Boc mass, −100).

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

实验步骤: Following the procedure of Example 5(c) 3-(4-cyano phenoxy)-5-phenethyloxy benzoic acid 0.6 g (1.66 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.378 g, 1.66 mmol) were used to afford 0.55 g of the required product. 1H NMR (DMSO-d6): δ 1.05 (3H, m), 1.4 (9H, s), 1.55 (2H, m), 1.7 (1H, m), 2.1 (5H, s), 3.0 (5H, m), 4.2 (2H, t), 4.4 (1H, m), 6.62 (1H, s), 6.78 (2H, s), 7.14 (2H, d), 7.24 (1H, m), 7.3 (4H, d), 7.88 (2H, d).

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

实验步骤: Following the procedure of Example 5(c) 3-(4-cyano phenoxy)-5-phenethyloxy benzoic acid 0.6 g (1.66 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.378 g, 1.66 mmol) were used to afford 0.55 g of the required product. 1H NMR (DMSO-d6): δ 1.05 (3H, m), 1.4 (9H, s), 1.55 (2H, m), 1.7 (1H, m), 2.1 (5H, s), 3.0 (5H, m), 4.2 (2H, t), 4.4 (1H, m), 6.62 (1H, s), 6.78 (2H, s), 7.14 (2H, d), 7.24 (1H, m), 7.3 (4H, d), 7.88 (2H, d).

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

实验步骤: 6-(4-cyano phenoxy)-5-fluoro-2-(3-trifluoromethoxy phenoxy)nicotinic acid (1.3 g, 2.99 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.684 g, 3.0 mmol) were coupled using the procedure of Example 5(c) to afford 1.1 g of the required product. 1HNMR (DMSO-d6): δ 1.2 (2H, m), 1.4 (9H, d), 1.5 (2H, m), 1.6 (2H, m), 2.2 (1H, m), 2.35 (1H, m), 3.0 (3H, m), 3.7 (1H, m), 4.45 (1H, m), 6.78 (1H, m), 7.18 (1H, m), 7.26 (2H, m), 7.32 (1H, s), 7.46 (1H, m), 7.76 (1H, m), 7.86 (1H, s), 8.1 (1H, m).

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

实验步骤: 2-(4-cyano phenoxy)-6-(4-trifluoromethoxy phenoxy)nicotinic acid (0.2 g, 0.48 mmol) and (2-Piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.11 g, 0.48 mmol) were coupled using the procedure of Example 5(c) to afford 0.21 g of the required product. Percentage purity (LCMS): 68.11%.

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

实验步骤: 6-(4-cyano phenoxy)-2-(4-fluoro phenoxy)nicotinic acid (0.2 g, 0.57 mmol) and (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.13 g, 0.57 mmol) were coupled using the procedure of Example 5(c) to afford 0.25 g of the required product. Percentage purity: LCMS (−ve mode): 67.5%.