ethyl piperidine-4-carboxylate;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (5.5 mL, 0.5 M in EtOH) was added to a mixture of 6-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-1H-indole-3-carbaldehyde (D102) (200 mg) and piperidine-4-carboxylic acid ethyl ester hydrochloride (507 mg). The reaction mixture was stirred at room temperature for 10 mins, and AcOH (0.5 ml) was added. After the solvent was evaporated, the residue was dissolved in DCM (40 mL). NaBH(OAc)3 (554 mg) was then added in one portion. After stirred overnight, the reaction was quenched with saturated aqueous sodium bicarbonate solution, and extracted with DCM for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by Mass Directed AutoPrep to afford ethyl 1-{[6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-4-piperidinecarboxylate (D103) (140 mg) as a white solid. MS (ES): C27H30ClN5O4 requires 523; found 524.2. After the solvent was evaporated the residue was dissolved in DCM (40 mL) NaBH(OAc)3 (554 mg) was then added in one portion After stirred overnight the reaction was quenched with saturated aqueous sodium bicarbonate solution extracted with DCM for 3 times The combined organic solution was washed with brine dried over anhydrous sodium sulfate The dried solution was concentrated The residue was purified by Mass Directed AutoPrep

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 4-piperidinecarboxylate hydrochloride (969 mg) and 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde (D61) (396 mg) was added to a solution of NaOH (200 mg) in ethanol (10 mL). After stirring for 0.5 hour, ethanol was evaporated off and then dichloromethane (40 mL) containing AcOH (0.5 mL) was added to the residue. NaBH(OAc)3 (1.06 g) was added to the above mixture. The reaction mixture was stirred at room temperature overnight and then terminated by saturated NaHCO3 solution. The organic layer was separated and washed with water and brine. After the solvent was evaporated off the residue was purified by Mass Directed AutoPrep to afford ethyl 1-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylate (D79) (308 mg) as a yellow solid. MS (ES): C29H33ClN4O4 requires 536; found 537.3 (M+H+). ethanol was evaporated off dichloromethane (40 mL) containing AcOH (0.5 mL) was added to the residue NaBH(OAc)3 (1.06 g) was added to the above mixture The reaction mixture was stirred at room temperature overnight terminated by saturated NaHCO3 solution The organic layer was separated washed with water and brine After the solvent was evaporated off the residue was purified by Mass Directed AutoPrep