2-[4-(aminomethyl)phenyl]ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using the EDCI coupling general procedure F: Reaction of 2-(4-Aminomethyl-phenyl)-ethanol (306 mg, 2.03 mmol), 3,5-dichloroisonicotinic acid (385 mg, 2.03 mmol), 1-hydroxybenzotriazole (301 mg, 2.22 mmol), 4-methyl morpholine (0.50 mL, 4.45 mmol), and EDCI (426 mg, 2.22 mmol) in anhydrous DMF (5 mL) overnight at room temperature and overnight at 40° C. followed by column chromatography on silica gel (2:2:96 MeOH—NH4OH—CH2Cl2) gave the title compound (291 mg, 44%) as a white foam. overnight at 40° C.

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of NH3/EtOH (170 mL) was added (4-Bromomethyl-phenyl)-acetic acid (1.61 g, 7.01 mmol). The resultant solution was stirred at room temperature for 2 h. The mixture was concentrated in vacuo, and redissolved with anhydrous THF (10 mL). To the solution, BH3.Me2S was added, and the mixture was stirred for 1 h at 70° C., and at room temperature for 2 d. The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added, and the mixture was stirred at 70° C. for 1 h. Water (20 mL) was added, and it was neutralized with 1 N NaOH to pH˜7. The solution was concentrated to dryness under high vacuum, washed with MeOH/CH2Cl2, and filtered. The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2) to afford the title compound (820 mg, 77%) as a white foam. The mixture was concentrated in vacuo redissolved with anhydrous THF (10 mL) Me2S was added at room temperature for 2 d The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added the mixture was stirred at 70° C. for 1 h Water (20 mL) was added The solution was concentrated to dryness under high vacuum washed with MeOH/CH2Cl2 filtered The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of NH3/EtOH (170 mL) was added (4-Bromomethyl-phenyl)-acetic acid (1.61 g, 7.01 mmol). The resultant solution was stirred at room temperature for 2 h. The mixture was concentrated in vacuo, and redissolved with anhydrous THF (10 mL). To the solution, BH3.Me2S was added, and the mixture was stirred for 1 h at 70° C., and at room temperature for 2 d. The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added, and the mixture was stirred at 70° C. for 1 h. Water (20 mL) was added, and it was neutralized with 1 N NaOH to pH˜7. The solution was concentrated to dryness under high vacuum, washed with MeOH/CH2Cl2, and filtered. The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2) to afford the title compound (820 mg, 77%) as a white foam. The mixture was concentrated in vacuo redissolved with anhydrous THF (10 mL) Me2S was added at room temperature for 2 d The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added the mixture was stirred at 70° C. for 1 h Water (20 mL) was added The solution was concentrated to dryness under high vacuum washed with MeOH/CH2Cl2 filtered The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-[4-(2-Hydroxyethyl)benzyl]-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide was prepared from 2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid and 4-(2-hydroxyethyl)benzylamine using method H. NMR; δH [2H6]—DMSO 9.11,(1H, t), 7.99,(2H, d), 7.89,(1H, dd), 7.76,(1H, d), 7.56-7.51,(3H, m), 7.24,(2H, d), 7.16,(2H, d), 4.62,(1H, t), 4.46,(2H, d), 3.55,(2H, q), 2.69,(2H, t), 2.56,(3H, s), 2.31,(3H, s). LCMS; retention time 3.00 min, MH+ 428.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-[4-(2-Hydroxyethyl)benzyl]-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide was prepared from 2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid and 4-(2-hydroxyethyl)benzylamine using method H. NMR; δH [2H6]—DMSO 9.11,(1H, t), 7.99,(2H, d), 7.89,(1H, dd), 7.76,(1H, d), 7.56-7.51,(3H, m), 7.24,(2H, d), 7.16,(2H, d), 4.62,(1H, t), 4.46,(2H, d), 3.55,(2H, q), 2.69,(2H, t), 2.56,(3H, s), 2.31,(3H, s). LCMS; retention time 3.00 min, MH+ 428.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using the EDCI coupling general procedure F: Reaction of 2-(4-Aminomethyl-phenyl)-ethanol (306 mg, 2.03 mmol), 3,5-dichloroisonicotinic acid (385 mg, 2.03 mmol), 1-hydroxybenzotriazole (301 mg, 2.22 mmol), 4-methyl morpholine (0.50 mL, 4.45 mmol), and EDCI (426 mg, 2.22 mmol) in anhydrous DMF (5 mL) overnight at room temperature and overnight at 40° C. followed by column chromatography on silica gel (2:2:96 MeOH—NH4OH—CH2Cl2) gave the title compound (291 mg, 44%) as a white foam. overnight at 40° C.

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of NH3/EtOH (170 mL) was added (4-Bromomethyl-phenyl)-acetic acid (1.61 g, 7.01 mmol). The resultant solution was stirred at room temperature for 2 h. The mixture was concentrated in vacuo, and redissolved with anhydrous THF (10 mL). To the solution, BH3.Me2S was added, and the mixture was stirred for 1 h at 70° C., and at room temperature for 2 d. The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added, and the mixture was stirred at 70° C. for 1 h. Water (20 mL) was added, and it was neutralized with 1 N NaOH to pH˜7. The solution was concentrated to dryness under high vacuum, washed with MeOH/CH2Cl2, and filtered. The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2) to afford the title compound (820 mg, 77%) as a white foam. The mixture was concentrated in vacuo redissolved with anhydrous THF (10 mL) Me2S was added at room temperature for 2 d The reaction was concentrated in vacuo, 6 N HCl (10 mL) was added the mixture was stirred at 70° C. for 1 h Water (20 mL) was added The solution was concentrated to dryness under high vacuum washed with MeOH/CH2Cl2 filtered The crude product was purified by flash chromatography on silica gel (5:3:92 CH3OH—NH3 H2O—CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 0.74 g (0.005 mol) of p-cyanophenethyl alcohol in 50 ml of ethanol containing 10 ml of concentrated hydrochloric acid was hydrogenated at 30 psi using 0.1 g 5% Pd/C for 72 hours. The catalyst was removed by filtration and the solvent was removed under reduced pressure. for 72 hours The catalyst was removed by filtration the solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-(2-Hydroxyethyl)phenylmethylamine and tert-butyl 3-(4-chlorophenyl)-2-hydroxyimino-3-oxopropionate are dissolved in pyridine, and the mixture is treated in the same manner as in Starting Material Synthetic Example 170 to give the objective tert-butyl 5-(4-chlorophenyl)-2-[4-(2-hydroxyethyl)phenyl]imidazole-4-carboxylate. the mixture is treated in the same manner as

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 0.74 g (0.005 mol) of p-cyanophenethyl alcohol in 50 ml of ethanol containing 10 ml of concentrated hydrochloric acid was hydrogenated at 30 psi using 0.1 g 5% Pd/C for 72 hours. The catalyst was removed by filtration and the solvent was removed under reduced pressure. for 72 hours The catalyst was removed by filtration the solvent was removed under reduced pressure