4-甲氧基哌啶盐酸盐

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

实验步骤: This compound was prepared by using procedures analogous to those described for the synthesis of Example 54, Step 3 starting from 2-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)propanoic acid and 4-methoxypiperidine hydrochloride (Matrix and Cat. No. 015567). LCMS (M+H)+: m/z=571.3. This compound was prepared

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

实验步骤: Compound 531 (120 mg, 0.300 mmol) and 4-methoxypiperidine hydrochloride (139 mg, 0.900 mmol) were suspended in THF (4 mL), and triethylamine (0.140 mL, 0.990 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1), followed by reslurrying with a mixed solvent of diisopropyl ether and diethyl ether to afford the entitled Compound 545 (96.0 mg, 74%) as a white solid. The reaction mixture was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1)

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

实验步骤: To a solution of 1-t-butoxycarbonyl-4-methoxypiperidine (2.84 g) in ethyl acetate (20 ml) was added 4N hydrochloric-acid-ethyl acetate solution (20 ml) and the mixture was stirred at ambient temperature for 1 hour. The solution was evaporated in vacuo to give 4-methoxypiperidine hydrochloride as a colorless amorphous powder (2.03 g). The solution was evaporated in vacuo

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [3-(2-Chloropyrimidin-5-yl)phenyl]methanol (200 mg) was mixed with DMF (4 ml), and 4-methoxypiperidine hydrochloride (180 mg) and potassium carbonate (500 mg) were added thereto, followed by stirring at 70° C. for 5 hours. The reaction mixture was concentrated under reduced pressure, and CHCl3 and a saturated aqueous sodium hydrogen carbonate solution were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain {3-[2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl]phenyl}methanol (249 mg). were added The reaction mixture was concentrated under reduced pressure, and CHCl3 a saturated aqueous sodium hydrogen carbonate solution were then added The organic layer was dried over Na2SO4 concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

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

实验步骤: To a solution of 4-methoxypiperidine-1-carboxylic acid tert-butyl ester (Preparation 67, 1.58 g, 7.34 mmol) in methanol (20 mL) was added hydrochloric acid in 1,4-dioxane (4M, 10 mL) and the mixture stirred for 3 h at rt. Concentration in vacuo gave an oil which was redissolved in water (100 mL). The aqueous layer was washed with ethyl acetate (2×30 mL) and concentrated to give the title compound as colourless solid. δH (D2O): 1.80, 2.14 (4H, 2m), 3.13 (2H, m), 3.38 (2H, m), 3.40 (3H, s), 3.68 (m, 1H). Concentration in vacuo gave an oil which The aqueous layer was washed with ethyl acetate (2×30 mL) 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 in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 4-methoxypiperidine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 1.14-1.32 (m, 3 H) 1.63-1.93 (m, 5 H) 1.96-2.10 (m, 2 H) 2.44 (s, 3 H) 3.22 (t, J=6.3 Hz, 2 H) 7.67 (d, J=7.6 Hz, 1 H) 7.74 (s, 1 H) 7.81 (br. s., 1 H) 8.25 (br. s., 1 H) 8.43 (br. s., 1 H) 8.57 (br. s., 1 H) 8.78 (br. s., 1 H) 8.91-8.94 (m, 1 H) 13.25 (br. s., 1 H). MS m/z [M+H]+ 418.4.

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 in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 4-methoxypiperidine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 1.14-1.32 (m, 3 H) 1.63-1.93 (m, 5 H) 1.96-2.10 (m, 2 H) 2.44 (s, 3 H) 3.22 (t, J=6.3 Hz, 2 H) 7.67 (d, J=7.6 Hz, 1 H) 7.74 (s, 1 H) 7.81 (br. s., 1 H) 8.25 (br. s., 1 H) 8.43 (br. s., 1 H) 8.57 (br. s., 1 H) 8.78 (br. s., 1 H) 8.91-8.94 (m, 1 H) 13.25 (br. s., 1 H). MS m/z [M+H]+ 418.4.

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 in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 4-methoxypiperidine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 1.14-1.32 (m, 3H) 1.63-1.93 (m, 5H) 1.96-2.10 (m, 2H) 2.44 (s, 3H) 3.22 (t, J=6.3 Hz, 2H) 7.67 (d, J=7.6 Hz, 1H) 7.74 (s, 1H) 7.81 (br. s., 1H) 8.25 (br. s., 1H) 8.43 (br. s., 1H) 8.57 (br. s., 1H) 8.78 (br. s., 1H) 8.91-8.94 (m, 1H) 13.25 (br. s., 1H). MS m/z [M+H]+ 418.4.

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

实验步骤: This compound was prepared by using procedures analogous to those described for the synthesis of Example 54, Step 3 starting from 2-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)propanoic acid and 4-methoxypiperidine hydrochloride (Matrix and Cat. No. 015567). LCMS (M+H)+: m/z=571.3. This compound was prepared

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

实验步骤: This compound was prepared by using procedures analogous to those described for the synthesis of Example 54, Step 3 starting from 2-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)propanoic acid and 4-methoxypiperidine hydrochloride (Matrix and Cat. No. 015567). LCMS (M+H)+: m/z=571.3. This compound was prepared

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

实验步骤: Compound 531 (120 mg, 0.300 mmol) and 4-methoxypiperidine hydrochloride (139 mg, 0.900 mmol) were suspended in THF (4 mL), and triethylamine (0.140 mL, 0.990 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1), followed by reslurrying with a mixed solvent of diisopropyl ether and diethyl ether to afford the entitled Compound 545 (96.0 mg, 74%) as a white solid. The reaction mixture was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1)

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

实验步骤: Compound 531 (120 mg, 0.300 mmol) and 4-methoxypiperidine hydrochloride (139 mg, 0.900 mmol) were suspended in THF (4 mL), and triethylamine (0.140 mL, 0.990 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1), followed by reslurrying with a mixed solvent of diisopropyl ether and diethyl ether to afford the entitled Compound 545 (96.0 mg, 74%) as a white solid. The reaction mixture was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (chloroform:methanol=49:1)