N-cyclohexylpiperidine-4-carboxamide;hydrochloride

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

実験手順: The title compound is prepared according to the reaction 3.01c described above using 4-chloro-pyridine-2-carboxaldehyde and piperidine-4-carboxylic acid cyclohexylamide hydrochloride as in 3.01c: LC-MS A: tR=0.58 min; [M+H]+=380.19.

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

実験手順: The title compound is prepared according to the reaction 3.01c described above using 5-bromo-pyridine-3-carboxaldehyde and piperidine-4-carboxylic acid cyclohexylamide hydrochloride as in 3.01c: LC-MS A: tR=0.58 min; [M+H]+=380.19.

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

実験手順: The title compound is prepared according to the reaction 3.01c described above using 6-bromo-pyridine-2-carboxaldehyde and piperidine-4-carboxylic acid cyclohexylamide hydrochloride as in 3.01c: LC-MS A: tR=0.61 min; [M+H]+=382.20.

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

実験手順: A mixture of 2-bromo-4-formylpyridine (1 g, 5.38 mmol), piperidine-4-carboxylic acid cyclohexylamide hydrochloride J-1 (1.327 g, 5.38 mmol) and DIPEA (2.78 mL, 16.13 mmol) in DCM (25 mL) is treated with sodium triacetoxy borohydride (2.28 g, 10.75 mmol) in 5 portions over 20 min. and the reaction mixture is stirred for 18 h at RT. Aq. sat. NaHCO3 (25 mL) is added and the mixture is stirred for 30 min. The phases are separated and the aqueous phase is extracted twice with DCM (25 mL). The combined organic phases are dried over MgSO4 and evaporated. The crude residue is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:4 to EtOAc 100%. After concentration of the product-containing fractions, the title compound (1.18 g, 58%) is obtained as a colorless solid LC-MS A: tR=0.59 min; [M+H]+=382.15. the mixture is stirred for 30 min The phases are separated the aqueous phase is extracted twice with DCM (25 mL) The combined organic phases are dried over MgSO4 evaporated The crude residue is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:4 to EtOAc 100%

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-cyclohexylcarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (21.11 g, 68 mmol) in dioxane (250 mL) is treated with a 4M HCl solution in dioxane (51 ml, 204 mmol) at 0° C. for 1 h. The reaction mixture is stirred at 50° C. for 4 h. The resulting suspension is cooled down to RT and the product filtered, washed with cold dioxane (50 mL) and dried under HV. The subtitle compound (16.64 g, 99%) is obtained as a white powder; LC-MS A: tR=0.46 min; [M+H]+=211.20. The resulting suspension is cooled down to RT the product filtered washed with cold dioxane (50 mL) dried under HV

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

実験手順: A solution of α-ethyl-3-nitro-benzenemethanol (0.54 g, 2.98 mmol) in DCM (10 mL) is treated with PPh3 (1.6 g, 6.1 mmol).) and CBr4 (2 g, 6.03 mmol). The yellowish solution is stirred at RT for 2 h 30. Piperidine-4-carboxylic acid cyclohexylamide hydrochloride J-1 (0.82 g) is added at once, as well as DIPEA (2 mL). The RM is stirred at RT overnight then heated to 70° C. for 1H. The RM is evaporated under reduced pressure. The residue is partitioned between DCM (25 mL) and sat. aq. NaHCO3 (25 mL). The organic layer is washed twice with sat. aq. NaHCO3, dried over MgSO4 and evaporated under reduced pressure. The crude residue is purified by flash chromatography on silica gel using a gradient of DCM/MeOH/NH4OH 95:5:1 to 90:10:1. After concentration of the product-containing fractions, the title compound (0.173 g, 16%) is obtained as a colorless solid LC-MS A: tR=0.68 min; [M+H]+=374.21. The RM is stirred at RT overnight then heated to 70° C. for 1H The RM is evaporated under reduced pressure The residue is partitioned between DCM (25 mL) and sat. aq. NaHCO3 (25 mL) The organic layer is washed twice with sat. aq. NaHCO3 dried over MgSO4 evaporated under reduced pressure The crude residue is purified by flash chromatography on silica gel using a gradient of DCM/MeOH/NH4OH 95:5:1 to 90:10:1